Pair Name	Baicalein, Docetaxel
Phytochemical Name	Baicalein
Anticancer drug Name	Docetaxel
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Baicalein enhances the antitumor efficacy of docetaxel on nonsmall cell lung cancer in a β-catenin-dependent manner

Pair Name	Crocin, Fluorouracil
Phytochemical Name	Crocin
Anticancer drug Name	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	We demonstrated an antitumor activity of crocin in CRC and its potential role in improvement of inflammation with mucosal ulcers and high-grade dysplastic crypts, supporting the desireability of further investigations on the therapeutic potential of this approach in CRC.

Pair Name	Curcumin, Quinacrine
Phytochemical Name	Curcumin
Anticancer drug Name	Quinacrine
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Quinacrine and Curcumin in combination decreased the breast cancer angiogenesis by modulating ABCG2 via VEGF A

Pair Name	Kuromanin chloride, Cisplatin
Phytochemical Name	Kuromanin chloride
Anticancer drug Name	Cisplatin
Disease Info	[ICD-11: 2C77]	Cervical cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Cyanidin-3-O-glucoside and cisplatin inhibit proliferation and downregulate the PI3K/AKT/mTOR pathway in cervical cancer cells

Pair Name	Magnoflorine, Doxorubicin
Phytochemical Name	Magnoflorine
Anticancer drug Name	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Magnoflorine improves sensitivity to doxorubicin (DOX) of breast cancer cells via inducing apoptosis and autophagy through AKT/mTOR and p38 signaling pathways

Pair Name	Ononin, Paclitaxel
Phytochemical Name	Ononin
Anticancer drug Name	Paclitaxel
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our findings suggested that the therapeutic index of PTX-based chemotherapy could be improved by reducing toxicity with increasing antitumor capabilities when combined with ononin.

Pair Name	Polydatin, 2-Deoxy-d-glucose
Phytochemical Name	Polydatin
Anticancer drug Name	2-Deoxy-d-glucose
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Our study demonstrates that PD synergised with 2-DG to enhance its anti-cancer efficacy by inhibiting the ROS/PI3K/AKT/HIF-1α/HK2 signalling axis, providing a potential anti-cancer strategy.

Pair Name	Silibinin, Regorafenib
Phytochemical Name	Silibinin
Anticancer drug Name	Regorafenib
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	The present study suggests that silybin in combination with regorafenib is a promising strategy for treatment of metastatic colorectal patients.

Pair Name	Tanshinone IIA, Doxorubicin
Phytochemical Name	Tanshinone IIA
Anticancer drug Name	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Tan IIA could be used as a novel agent combined with Dox in breast cancer therapy.

Pair Name	Trifolirhizin, Sorafenib
Phytochemical Name	Trifolirhizin
Anticancer drug Name	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Synergistic anticancer effect of flavonoids from Sophora alopecuroides with Sorafenib against hepatocellular carcinoma

Pair Name	Withaferin A, Oxaliplatin
Phytochemical Name	Withaferin A
Anticancer drug Name	Oxaliplatin
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These results support the notion that combination treatment with oxaliplatin and WA could facilitate development of an effective strategy for PC treatment.

Pair Name	(S)-10-Hydroxycamptothecin, Crizotinib
Phytochemical	(S)-10-Hydroxycamptothecin
Drug	Crizotinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Development of 10-Hydroxycamptothecin-crizotinib conjugate based on the synergistic effect on lung cancer cells

Pair Name	[6]-Gingerol, Cisplatin
Phytochemical	[6]-Gingerol
Drug	Cisplatin
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	[6]-Gingerol enhances the cisplatin sensitivity of gastric cancer cells through inhibition of proliferation and invasion via PI3K/AKT signaling pathway

Pair Name	2,3,5,6-Tetramethylpyrazine, Doxorubicin
Phytochemical	2,3,5,6-Tetramethylpyrazine
Drug	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	DLJ14 and Adr combination treatment may inhibit proliferation of Adr-resistant human breast cancer cells through inhibition of the EGFR/PI3K/Akt survival pathway and induction of apoptosis via the mitochondrial-mediated apoptosis pathway.

Pair Name	4'-Hydroxywogonin, Wortmannin
Phytochemical	4'-Hydroxywogonin
Drug	Wortmannin
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	4'-HW decreased the viability and reduced angiogenesis in CRC, which was associated with downregulation of VEGF-A expression by disrupting the PI3K/AKT pathway. Our discoveries suggested 4'-HW as a promising anticancer agent against CRC targeting angiogenesis.

Pair Name	All-trans retinoic acid, Midostaurin
Phytochemical	All-trans-retinoic acid
Drug	Midostaurin
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Combination of midostaurin and ATRA exerts dose-dependent dual effects on acute myeloid leukemia cells with wild type FLT3

Pair Name	Aloe emodin, Gefitinib
Phytochemical	Aloe emodin
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	AE could enhance the gefitinib sensitivity of PC9-GR cells and reverse EMT by blocking PI3K/Akt/TWIS1 signal pathway.

Pair Name	Aloin, Irinotecan
Phytochemical	Aloin
Drug	Irinotecan
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our findings suggests that CPT-11 and Aloin are potential combination treatment partners against colorectal cancer. MicroRNA-133b may serve as a co-therapeutic target with IGF1R against colorectal cancer, which might overcome the existing treatment limitations.

Pair Name	Aloin, Metformin
Phytochemical	Aloin
Drug	Metformin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Activity
Result	Our research demonstrated that the concomitant treatment with aloin and MET enhances the antitumor effect by inhibiting the growth and invasion as well as inducing apoptosis and autophagy in HCC through PI3K/AKT/mTOR pathway.

Pair Name	Alpha-Hederin, Carboplatin
Phytochemical	Alpha-Hederin
Drug	Carboplatin
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Chemopreventive effect of α-hederin/carboplatin combination against experimental colon hyperplasia and impact on JNK signaling

Pair Name	alpha-Hydroxylinoleic acid, Paclitaxel
Phytochemical	alpha-Hydroxylinoleic acid
Drug	Paclitaxel
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	The safety profile of ABTL0812 and its good synergy with chemotherapy potentiate the therapeutic potential of current lines of treatment based on chemotherapy regimens, arising as a promising option for improving these patients therapeutic expectancy.

Pair Name	alpha-Mangostin, Sorafenib
Phytochemical	alpha-Mangostin
Drug	Sorafenib
Disease Info	[ICD-11: 2C30]	Melanoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These data demonstrate an unanticipated synergy between α-Mangostin and sorafenib, with mechanistic actions that convert a known safe natural product to a candidate combinatorial therapeutic agent.

Pair Name	Apigenin, Doxorubicin
Phytochemical	Apigenin
Drug	Doxorubicin
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Co-administration of apigenin with doxorubicin enhances anti-migration and antiproliferative effects via PI3K/PTEN/AKT pathway in prostate cancer cells

Pair Name	Apigenin, TNF-related apoptosis inducing ligand
Phytochemical	Apigenin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2D10.Z]	Thyroid cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Apigenin synergizes with TRAIL through regulation of Bcl2 family proteins in inducing cytotoxicity, and suppression of AKT potentiates synergistic cytotoxicity of apigenin with TRAIL in ATC cells

Pair Name	Apigenin, TNF-related apoptosis inducing ligand
Phytochemical	Apigenin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Apigenin enhances TRAIL-induced antitumor activity in NSCLC cells by APG via inhibition of the NF-kappaB, AKT and ERK prosurvival regulators

Pair Name	Astragaloside IV, Bevacizumab
Phytochemical	Astragaloside IV
Drug	Bevacizumab
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	This paper demonstrates that AST-IV enhances the effect of BV on inhibiting proliferation and promoting apoptosis of lung adenocarcinoma cells through inhibiting autophagy pathway.

Pair Name	Astragaloside IV, Carboplatin
Phytochemical	Astragaloside IV
Drug	Carboplatin
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our results suggested that AgIV enhanced carboplatin sensitivity in prostate cancer cell lines by suppressing AKT/NF-κB signaling, thus suppressed epithelial-mesenchymal transition induced by carboplatin. Our findings provided a new mechanism for AgIV in overcoming drug resistance of platinum-based chemotherapy and suggested a potential combination therapy of AgIV and carboplatin in prostate cancer.

Pair Name	Baicalein, Cisplatin
Phytochemical	Baicalein
Drug	Cisplatin
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Baicalein enhanced cisplatin sensitivity of gastric cancer cells by inducing cell apoptosis and autophagy via Akt/mTOR and Nrf2/Keap 1 pathway

Pair Name	Baicalein, Cisplatin
Phytochemical	Baicalein
Drug	Cisplatin
Disease Info	[ICD-11: 2C73]	Ovarian cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Treatment with baicalein improved the sensitivity of ovarian cancer cells to cisplatin and inhibited cell proliferation, metastasis and tumor growth

Pair Name	Berbamine, Arcyriaflavin A
Phytochemical	Berbamine
Drug	Arcyriaflavin A
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our findings suggest that a novel combination therapy involving berbamine and ArcA could effectively eradicate glioblastoma stem-like cells.

Pair Name	Berberine, Erlotinib
Phytochemical	Berberine
Drug	Erlotinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our data supported use of BBR in combination with erlotinib as a novel strategy for treatment of patients with EGFR positive tumors.

Pair Name	Beta-Elemene, Fluorouracil
Phytochemical	Beta-Elemene
Drug	Fluorouracil
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The conclusion obtained, considering that the results suggest that the combination may be important specifically in the treatment of TNBC.

Pair Name	Beta-Elemene, Rapamycin
Phytochemical	Beta-Elemene
Drug	Rapamycin
Disease Info	[ICD-11: 2A83]	Multiple myeloma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	We demonstrate that the novel combination of mTOR inhibitor with β-elemene synergistically attenuates tumor cell growth in follicular thyroid cancer, which requires additional preclinical validation.

Pair Name	Beta-Elemene, Temozolomide
Phytochemical	Beta-Elemene
Drug	Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	These results revealed that β-elemene could significantly increase the radiosensitivity and chemosensitivity of GBM. β-elemene may be used as a potential drug in combination with the radiotherapy and chemotherapy of GBM

Pair Name	Beta-Sitosterol, Gemcitabine
Phytochemical	Beta-Sitosterol
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	β-Sitosterol and Gemcitabine Exhibit Synergistic Anti-pancreatic Cancer Activity by Modulating Apoptosis and Inhibiting Epithelial-Mesenchymal Transition by Deactivating Akt/GSK-3β Signaling

Pair Name	Betulinic Acid, Sorafenib
Phytochemical	Betulinic Acid
Drug	Sorafenib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	We showed that combination therapy with low concentrations of sorafenib and betulinic acid had the capacity to induce high levels of cell death and abolish clonogenic activity in some NSCLC cell lines regardless of KRAS mutations.

Pair Name	Betulinic Acid, Sorafenib
Phytochemical	Betulinic Acid
Drug	Sorafenib
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	We showed that combined treatment with low concentrations of sorafenib and betulinic acid had the capacity to inhibit proliferation and abolish clonogenic activity in PDAC cell lines.

Pair Name	Biochanin A, Fluorouracil
Phytochemical	Biochanin A
Drug	Fluorouracil
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	The synergistic antitumor effect of Bio-A/ 5-FU combination can be, at least partly, attributed to Bio-A-mediated suppression of ER-α/Akt axis and the augmentation of 5-FU-mediated proapoptotic effects.

Pair Name	Biochanin A, Temozolomide
Phytochemical	Biochanin A
Drug	Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Chanin A significantly enhanced the anticancer efficacy of temozolomide in GBM cells.

Pair Name	Bisdemethoxycucurmin, Icotinib
Phytochemical	Bisdemethoxycucurmin
Drug	Icotinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our data indicate that BMDC has the potential to improve the treatment of primary EGFR-TKI resistant NISCLC that cannot be controlled with single-target agent, such as icotinib.

Pair Name	Bufalin, Hydroxycamptothecin
Phytochemical	Bufalin
Drug	Hydroxycamptothecin
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The present study suggested that the combination of bufalin and hydroxycampothecin improved the inhibitory effects of both drugs on CRPC tumors in vivo, potentially via the regulation of the PI3K/AKT/GSK-3β and p53-dependent apoptosis signaling pathways.

Pair Name	Bufalin, MK2206
Phytochemical	Bufalin
Drug	MK2206
Disease Info	[ICD-11: 2A83.1]	Plasma cell myeloma		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	The data suggested that MK2206 significantly enhanced the cytocidal effects of bufalin in MM cells, regardless of the sensitivity to bortezomib, via the inhibition of the AKT/mTOR pathway. The study provided the basis of a promising treatment approach for MM.

Pair Name	Bufalin, Vorinostat
Phytochemical	Bufalin
Drug	Vorinostat
Disease Info	[ICD-11: 2A00-2F9Z]	Solid tumour or cancer		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Activity
Result	These accumulating data might guide development of new breast and lung cancer therapies.

Pair Name	Capsaicin, Docetaxel
Phytochemical	Capsaicin
Drug	Docetaxel
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	We showed that the synergistic anti-proliferative effect may be attributed to two independent effects: Inhibition of the PI3K/Akt/mTOR signaling pathway by one side, and AMPK activation by the other. In vivo experiments confirmed the synergistic effects of docetaxel and capsaicin in reducing the tumor growth of PC3 cells.

Pair Name	Capsaicin, Erlotinib
Phytochemical	Capsaicin
Drug	Erlotinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These results may provide a rationale to combine capsaicin with erlotinib for lung cancer treatment.

Pair Name	Capsaicin, Fluorouracil
Phytochemical	Capsaicin
Drug	Fluorouracil
Disease Info	[ICD-11: 2C17]	Hepatocellular carcinoma		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These results demonstrate that capsaicin may be a useful adjunct therapy to improve chemosensitivity in CCA. This effect likely occurs via PI3K/AKT/mTOR pathway activation, suggesting a promising strategy for the development of combination drugs for CCA.

Pair Name	Celastrol, Tamoxifen
Phytochemical	Celastrol
Drug	Tamoxifen
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The Synergistic Effects of Celastrol in combination with Tamoxifen on Apoptosis and Autophagy in MCF-7 Cells

Pair Name	Cordycepin, Apatinib
Phytochemical	Cordycepin
Drug	Apatinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our findings demonstrated that the combination of cordycepin and apatinib has synergistically anticancer effect on NSCLC cells by down-regulating VEGF/PI3K/Akt signaling pathway. This result indicated that cordycepin and apatinib could be a promising drug combination against NSCLC.

Pair Name	Cordycepin, Cisplatin
Phytochemical	Cordycepin
Drug	Cisplatin
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	This study provides comprehensive evidence that cordycepin inhibits osteosarcoma cell growth and invasion and induces osteosarcoma cell apoptosis by activating AMPK and inhibiting the AKT/mTOR signaling pathway and enhances the sensitivity of osteosarcoma cells to cisplatin, suggesting that cordycepin is a promising treatment for osteosarcoma.

Pair Name	Costunolide, Doxorubicin
Phytochemical	Costunolide
Drug	Doxorubicin
Disease Info	[ICD-11: 2B33.3]	Acute lymphoblastic leukemia		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These results demonstrate that costunolide may be a potent therapeutic agent against chronic myeloid leukemia.

Pair Name	Costunolide, Osimertinib
Phytochemical	Costunolide
Drug	Osimertinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The combination of osimertinib and costunolide showed synergistic or additive inhibitory effects on tumor growth in osimertinib-resistant cell lines and PDX model. Hence, this study highlights a potential therapeutic strategy for osimertinib-resistant patients through targeting of MEK1 and AKT1/2 by costunolide.

Pair Name	Cryptotanshinone, Trifluridine
Phytochemical	Cryptotanshinone
Drug	Trifluridine
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	FTD combined with CTS has a synergistic anti-gastric cancer effect as shown by in vitro and in vivo experiments, and the combined treatment of FTD and CTS will be a promising treatment option for advanced gastric cancer.

Pair Name	Cucurbitacin B, Cisplatin
Phytochemical	Cucurbitacin B
Drug	Cisplatin
Disease Info	[ICD-11: 2C94]	Bladder cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our results showed that CuB may be a new agent that can support conventional treatment in bladder cancer. Our study is important in terms of enlightening new pathways and developing new treatment methods in the treatment of bladder cancer.

Pair Name	Curcumin, 2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
Phytochemical	Curcumin
Drug	2-(2-Amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Curcumin regulates the miR-21/PTEN/Akt pathway and acts in synergy with PD98059 to induce apoptosis of human gastric cancer MGC-803 cells

Pair Name	Curcumin, Docetaxel
Phytochemical	Curcumin
Drug	Docetaxel
Disease Info	[ICD-11: 2B70]	Esophageal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	CUR combined with DTX induced apoptosis and autophagy of ESCC and probably worked through the PI3K/AKT/mTOR signaling pathway. The combination of the autophagy inhibitor, CUR and DTX may become a new treatment strategy for esophageal cancer.

Pair Name	Curcumin, Nimustine
Phytochemical	Curcumin
Drug	Nimustine
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Curcumin potentiates the potent antitumor activity of ACNU against glioblastoma by suppressing the PI3K/AKT and NF-kappaB/COX-2 signaling pathways

Pair Name	Curcumin, TNF-related apoptosis inducing ligand
Phytochemical	Curcumin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Combined treatment with curcumin and carboplatin inhibited tumor cell growth, migration, and invasion compared with either drug alone. The synergistic antitumor activity of curcumin combined with carboplatin is mediated by multiple mechanisms involving suppression of NF-kappaB via inhibition of the Akt/IKKalpha pathway and enhanced ERK1/2 activity

Pair Name	Curcumin, Vemurafenib
Phytochemical	Curcumin
Drug	Vemurafenib
Disease Info	[ICD-11: 2C30]	Melanoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Curcumin suppresses cell proliferation and triggers apoptosis in vemurafenib-resistant melanoma cells by downregulating the EGFR signaling pathway

Pair Name	Daidzein, Gefitinib
Phytochemical	Daidzein
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Daidzein Synergizes with Gefitinib to Induce ROS/JNK/c-Jun Activation and Inhibit EGFR-STAT/AKT/ERK Pathways to enhance Lung Adenocarcinoma cells chemosensitivity

Pair Name	Daurinoline, Sorafenib
Phytochemical	Daurinoline
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our study provides insights into the molecular mechanisms underlying DS-induced inhibition of VM, which may facilitate the development of a novel clinical anti-HCC drug. Moreover, our findings suggest that the combination of DS and sorafenib constitutes a potential therapeutic strategy for HCC.

Pair Name	Emodin, Cytarabine
Phytochemical	Emodin
Drug	Cytarabine
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Emodin and its combination with Ara-C may be considered a promising therapeutic approach in AML and worthy of further investigation.

Pair Name	Emodin, Doxorubicin
Phytochemical	Emodin
Drug	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Emodin Interferes With AKT1-Mediated DNA Damage and Decreases Resistance of Breast Cancer Cells to Doxorubicin

Pair Name	Epsilon-Viniferin, alpha-Viniferin
Phytochemical	Epsilon-Viniferin
Drug	alpha-Viniferin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	ε-viniferin and α-viniferin may prove to be new approaches and effective therapeutic agents for osteosarcoma and lung cancer treatment.

Pair Name	Eriocalyxin B, Gemcitabine
Phytochemical	Eriocalyxin B
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Gem and EriB (or Isodon extract) taken together in combination regulated PDK1/AKT1/caspase and JNK signaling and promoted apoptosis synergistically, which may contribute to the much increased anti-proliferative activity compared to either agent alone.

Pair Name	Eurycomalactone, Cisplatin
Phytochemical	Eurycomalactone
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	This finding provides a rationale for the combined use of chemotherapy drugs with ECL to improve their efficacy in NSCLC treatment.

Pair Name	Fisetin, Fluorouracil
Phytochemical	Fisetin
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Fisetin and 5-fluorouracil: Effective combination for PIK3CA-mutant colorectal cancer

Pair Name	Fisetin, Sorafenib
Phytochemical	Fisetin
Drug	Sorafenib
Disease Info	[ICD-11: 2C30]	Melanoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Fisetin potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells.

Pair Name	Flavokawain A, Herceptin
Phytochemical	Flavokawain A
Drug	Herceptin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our results suggest FKA as a promising and novel apoptosis inducer and G2 blocking agent that, in combination with Herceptin, enhances for the treatment of HER2-overexpressing breast cancer.

Pair Name	Fucoxanthin, TNF-related apoptosis inducing ligand
Phytochemical	Fucoxanthin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C77]	Cervical cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	We found that fucoxanthin- or TRAIL-induced apoptosis of human cervical cancer cells was obviously down-regulated. CONCLUSIONS Taken together, these findings suggest that fucoxanthin and TRAIL increased the apoptosis in human cervical cancer cells by targeting the PI3K/Akt/NF-κB signaling pathway.

Pair Name	Fucoxanthin, TNF-related apoptosis inducing ligand
Phytochemical	Fucoxanthin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C77]	Cervical cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The findings of this study suggest that the combined use of fucoxanthin and TRAIL might be a useful strategy against TRAIL-resistant cervical cancer.

Pair Name	Furanodiene, Doxorubicin
Phytochemical	Furanodiene
Drug	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These observations indicate that furanodiene is a potential agent that may be utilized to improve the anticancer efficacy of doxorubicin and overcome the risk of chemotherapy in highly metastatic breast cancer.

Pair Name	Gambogenic acid, Erlotinib
Phytochemical	Gambogenic acid
Drug	Erlotinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our findings provide preclinical evidence for using GNA as an FGFR signaling pathway inhibitor to overcome erlotinib resistance in NSCLC treatment or to enhance erlotinib efficacy when used as a combined administration.

Pair Name	Gambogic Acid, Gemcitabine
Phytochemical	Gambogic Acid
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These results demonstrate that gambogic acid sensitizes pancreatic cancer cells to gemcitabine in vitro and in vivo by inhibiting the activation of the ERK/E2F1/RRM2 signaling pathway. The results also indicate that gambogic acid treatment combined with gemcitabine might be a promising chemotherapy strategy for pancreatic cancer.

Pair Name	Gamma-Tocotrienol, Cisplatin
Phytochemical	Gamma-Tocotrienol
Drug	Cisplatin
Disease Info	[ICD-11: 2C51]	Mesothelioma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These results suggest that the combination therapy of cisplatin with TRF is a plausible strategy for achieving tolerance for the chemotherapeutic agent in MM therapy.

Pair Name	Gamma-Tocotrienol, SU11274
Phytochemical	Gamma-Tocotrienol
Drug	SU11274
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Suggest that combined γ-tocotrienol and Met inhibitor treatment may provide benefit in treatment of breast cancers characterized by aberrant Met activity.

Pair Name	Garcinol, Cisplatin
Phytochemical	Garcinol
Drug	Cisplatin
Disease Info	[ICD-11: 2C73]	Ovarian cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our data demonstrated that garcinol has the potential to be used as an anticancer agent and may synergize the effect of DDP. These actions are most likely through the regulation of the PI3K/AKT and NF-κB pathways.

Pair Name	Gedunin, Epalrestat
Phytochemical	Gedunin
Drug	Epalrestat
Disease Info	[ICD-11: 2B66.Z]	Oral cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Our results provide compelling evidence that the combination of gedunin and epalrestat modulates expression of key oncogenic signalling kinases and transcription factors primarily by influencing phosphorylation and subcellular localisation. AR inhibitors such as gedunin and epalrestat are novel candidate agents for cancer prevention and therapy.

Pair Name	Genipin, Everolimus
Phytochemical	Genipin
Drug	Everolimus
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	These results reveal novel mechanisms through which UCP2 promotes cancer cell proliferation and support the combined inhibition of UCP2 and of Akt/mTOR pathway as a novel therapeutic strategy in the treatment of pancreatic adenocarcinoma.

Pair Name	Ginkgolide B, Cisplatin
Phytochemical	Ginkgolide B
Drug	Cisplatin
Disease Info	[ICD-11: 2B66.Z]	Oral cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These results suggest that PAFR is a therapeutic target for modulating CDDP sensitivity in OSCC cells. Thus, GB may be a novel drug that could enhance combination chemotherapy with CDDP for OSCC patients.

Pair Name	Ginsenoside compound K, Cisplatin
Phytochemical	Ginsenoside compound K
Drug	Cisplatin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Both CK and DDP can inhibit the proliferation, EMT, and induce the apoptosis in MCF-7 cells, which may be related to the PI3K/Akt pathway. In addition, the combination of CK with DDP can produce a better effect

Pair Name	Ginsenoside Rg1, Doxorubicin
Phytochemical	Ginsenoside Rg1
Drug	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	The present results support the chemosensitizing property of ginsenoside Rg1 in triple-negative breast cancer cell lines.

Pair Name	Ginsenoside Rg3, Endostar
Phytochemical	Ginsenoside Rg3
Drug	Endostar
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Endostar combined with ginsenoside Rg3 has stronger inhibiting effect on breast cancer tumor growth in tumor-bearing mice than single drug, and it can inhibit angiogenesis and cell invasion, and enhance cell autophagy.

Pair Name	Ginsenoside Rg3, Sorafenib
Phytochemical	Ginsenoside Rg3
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Rg3 has a synergistic effect on the sensitivity of HepG2 and Bel7404 hepatoma cells to SFN, which is related to HK2-mediated glycolysis and the PI3K/Akt signaling pathway.

Pair Name	Ginsenoside Rg3, Sorafenib
Phytochemical	Ginsenoside Rg3
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These findings suggest a promising strategy for HCC treatment, which could be performed in a sufficiently frequent manner.

Pair Name	Gossypol, Gefitinib
Phytochemical	Gossypol
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations.

Pair Name	Gossypol, Trastuzumab
Phytochemical	Gossypol
Drug	Trastuzumab
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	The trastuzumab/AT-101 combination may be a good candidate for patients with trastuzumab-resistant Her2-positive breast cancer and inhibition of the PI3K/AKT pathway may be one of the underlying mechanisms.

Pair Name	Guggulsterone, Gemcitabine
Phytochemical	Guggulsterone
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10.0]	Pancreatic ductal adenocarcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The combination of guggulsterone to gemcitabine enhanced antitumor efficacy through apoptosis induction by suppressing Akt and nuclear factor KappaB activity and by modulating apoptosis-related protein expression in pancreatic cancer

Pair Name	Halofuginone, Cisplatin
Phytochemical	Halofuginone
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Halofuginone Sensitizes Lung Cancer Organoids to Cisplatin via Suppressing PI3K/AKT and MAPK Signaling Pathways

Pair Name	Hesperetin, Cisplatin
Phytochemical	Hesperetin
Drug	Cisplatin
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Hesperetin could inhibit the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling pathway and induce the mitochondrial pathway via upregulating PTEN expression, thereby significantly enhancing DDP's anti-tumor effect on GC

Pair Name	Homoharringtonine, ACC010
Phytochemical	Homoharringtonine
Drug	ACC010
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	ACC010 and HHT cooperatively downregulated MYC and inhibited FLT3 activation. Further, when HHT was added, ACC010-resistant cells demonstrated a good synergy. We also extended our study to the mouse BaF3 cell line with FLT3-inhibitor-resistant FLT3-ITD/tyrosine kinase domain mutations and AML cells without FLT3-ITD. Collectively, our results suggested that the combination treatment of ACC010 and HHT might be a promising strategy for AML patients, especially those carrying FLT3-ITD.

Pair Name	Honokiol, Oxaliplatin
Phytochemical	Honokiol
Drug	Oxaliplatin
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	This combination allows a reduction in oxaliplatin dose, and thereby reduces its adverse effects. It may also enhance the chemotherapeutic effect of oxaliplatin for this disease.

Pair Name	Jervine, Decitabine
Phytochemical	Jervine
Drug	Decitabine
Disease Info	[ICD-11: 2A3Z]	Myelodysplastic syndrome		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	The Smo inhibitor jervine and its combination with decitabine have a synergistic effect on the proliferation, cell cycle, and apoptosis of MUTZ-1 cells, and its mechanism may be achieved by interfering with the Shh signaling pathway.

Pair Name	Kaempferol, Cisplatin
Phytochemical	Kaempferol
Drug	Cisplatin
Disease Info	[ICD-11: 2C73]	Ovarian cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Kaempferol Induces cell death in A2780 ovarian cancer cells and increases their sensitivity to cisplatin by activation of cytotoxic endoplasmic reticulum-mediated autophagy and inhibition of protein kinase B

Pair Name	Kaempferol, Erlotinib
Phytochemical	Kaempferol
Drug	Erlotinib
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These data imply that KAE may be a valid therapeutic candidate to potentiate PC cell sensitivity to ERL via inhibiting PI3K/AKT and EGFR signaling.

Pair Name	Kaempferol, Fluorouracil
Phytochemical	Kaempferol
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The present study demonstrated that kaempferol has a synergistic effect with 5‑FU by inhibiting cell proliferation and inducing apoptosis in colorectal cancer cells via suppression of TS or attenuation of p‑Akt activation. The combination of kaempferol and 5‑FU may be used as an effective therapeutic strategy for colorectal cancer.

Pair Name	lambda-Carrageenan Oligosaccharides, Fluorouracil
Phytochemical	lambda-Carrageenan Oligosaccharides
Drug	Fluorouracil
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These findings suggested that λ-COS could be used as an immune-modulating agent for chemotherapy.

Pair Name	Licochalcone B, TNF-related apoptosis inducing ligand
Phytochemical	Licochalcone B
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	LCB exhibits cytotoxic activity through modulation of the Akt/mTOR, ER stress and MAPK pathways in HCC cells and effectively enhances TRAIL sensitivity through the upregulation of DR5 expression in ERK- and JNK-dependent manner. Combination therapy with LCB and TRAIL may be an alternative treatment strategy for HCC.

Pair Name	Liquiritigenin, Cisplatin
Phytochemical	Liquiritigenin
Drug	Cisplatin
Disease Info	[ICD-11: 2C30]	Melanoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The results suggested that LQ plays an intensive role on CDDP suppressing invasion and metastasis through regulating the PI3 K/AKT signal pathway and suppressing the protein expression of MMP-2/9.

Pair Name	Liriodenine, Valproic acid
Phytochemical	Liriodenine
Drug	Valproic acid
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Liriodenine enhances the apoptosis effect of valproic acid in human colon cancer cells through oxidative stress upregulation and Akt inhibition

Pair Name	Luteolin, Erlotinib
Phytochemical	Luteolin
Drug	Erlotinib
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These findings suggest that combining luteolin with erlotinib offers a potential treatment strategy for glioblastoma multiforme IV.

Pair Name	Lycopene, Anti-PD-1 antibody
Phytochemical	Lycopene
Drug	Anti-PD-1 antibody
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	lycopene promoted anti-PD-1 therapeutic efficiency of lung cancer by promoting IFNγ-expressing CD8+ cells infiltrated in tumor tissues and increasing IFNγ expression in tumor cells.

Pair Name	Lycopene, Eicosapentaenoic acid
Phytochemical	Lycopene
Drug	Eicosapentaenoic acid
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our novel findings suggest that lycopene and EPA synergistically inhibited the growth of human colon cancer HT-29 cells even at low concentration. The inhibitory effects of lycopene and EPA on cell proliferation of human colon cancer HT-29 cells were, in part, associated with the down-regulation of the PI-3K/Akt/mTOR signaling pathway.

Pair Name	Lycopene, Enzalutamide
Phytochemical	Lycopene
Drug	Enzalutamide
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These results suggest that the enhanced antitumor effects of enzalutamide by lycopene may be related to the reduction of AR protein levels through lycopene-mediated inhibition of AKT/EZH2 pathway, which may provide a new approach to improve the efficacy of enzalutamide in CRPC.

Pair Name	Magnolin, B-RAF Inhibitors
Phytochemical	Magnolin
Drug	B-RAF Inhibitors
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Synergistic activity of magnolin combined with B-RAF inhibitor SB590885 in hepatocellular carcinoma cells via targeting PI3K-AKT/mTOR and ERK MAPK pathway

Pair Name	Matairesinol, Fluorouracil
Phytochemical	Matairesinol
Drug	Fluorouracil
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Matairesinol Induces Mitochondrial Dysfunction and Exerts Synergistic Anticancer Effects with 5-Fluorouracil in Pancreatic Cancer Cells

Pair Name	Myriocin, Cisplatin
Phytochemical	Myriocin
Drug	Cisplatin
Disease Info	[ICD-11: 2C30]	Melanoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	We suggest that myriocin is a novel potent anti-cancer agent that dually targets both VEGFR2 in ECs and IκBα in cancer cells, and exerts more pronounced anti-tumor effects than with either kinase being inhibited alone.

Pair Name	Naringenin, ABT-737
Phytochemical	Naringenin
Drug	ABT-737
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The combination of these drugs was found to further increase the cleavage of caspase-3 and poly ADP-ribose polymerase. Naringenin and ABT-737 also decreased Akt activation and increased p53 expression, suggesting the involvement of these pathways in the inhibition of gastric cell growth.

Pair Name	Naringenin, Cisplatin
Phytochemical	Naringenin
Drug	Cisplatin
Disease Info	[ICD-11: 2C77]	Cervical cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Effect of naringenin and its combination with cisplatin in cell death, proliferation and invasion of cervical cancer spheroids

Pair Name	Nobiletin, Vorinostat
Phytochemical	Nobiletin
Drug	Vorinostat
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The combination of nobiletin with vorinostat increased histone H3K9 and H3K27 acetylation levels in SCLC mouse tumor tissue and enhanced the expression of the BH3-only proteins BIM and BID. We conclude that nobiletin is a novel natural BH3 mimetic that can cooperate with vorinostat to induce apoptosis and autophagy in SCLC.

Pair Name	Norizalpinin, Fluorouracil
Phytochemical	Norizalpinin
Drug	Fluorouracil
Disease Info	[ICD-11: 2B70]	Esophageal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our results indicated that galangin played a synergistic anticancer role through NLRP3 inflammasome inhibition when paired with FU-5.

Pair Name	Noscapine, Cisplatin
Phytochemical	Noscapine
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our results suggest that Nos enhanced the anticancer activity of Cis in an additive to synergistic manner by activating multiple signaling pathways including apoptosis. These findings suggest potential benefit for use of Nos and Cis combination in treatment of lung cancer.

Pair Name	Oridonin, Arsenic oxide (As2O3)
Phytochemical	Oridonin
Drug	Arsenic oxide (As2O3)
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	The combination treatment induced ROS-dependent decrease in mitochondrial membrane potential (MMP) decrease, and relocation of Bax and cytochrome C. Besides, oridonin dramatically increased the intracellular Ca2+ overload triggered by As2O3. Furthermore, the co-treatment of oridonin and As2O3 induced ROS-mediated down-regulation of Akt and XIAP, and inhibition of NF-κB activation. The two drug combination enhanced tumor suppression activity in murine HCC model compared with single agent treatment in vivo.

Pair Name	Oridonin, Imatinib
Phytochemical	Oridonin
Drug	Imatinib
Disease Info	[ICD-11: 2B33.3]	Acute lymphoblastic leukemia		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Our data showed that oridonin remarkably suppressed activations of Akt/mTOR, Raf/MEK and STAT5 pathway in these primary specimens and oridonin with imatinib exerted synergetic suppressive effects on mTOR, STAT5 and LYN signaling in one imatinib resistant patient specimen. Additional evaluation of oridonin as a potential therapeutic agent for Ph+ ALL seems warranted.

Pair Name	Oridonin, Venetoclax
Phytochemical	Oridonin
Drug	Venetoclax
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Oridonin and venetoclax synergistically promote AML cell apoptosis by inhibiting AKT signaling.

Pair Name	OSW-1, Carboplatin
Phytochemical	OSW-1
Drug	Carboplatin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our data revealed the mode of action and molecular mechanism underlying the effect of OSW-1 against TNBC, and provided a useful guidance for improving the sensitivity of TNBC cells to conventional chemotherapeutic drugs, which warrants further investigation.

Pair Name	Oxidized tea polyphenol, Nimotuzumab
Phytochemical	Oxidized tea polyphenol
Drug	Nimotuzumab
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	OTP-3 can also serve as an effective therapeutic agent in NSCLC where it can augment the effects of nimotuzumab, a valuable property for combination agents.

Pair Name	Patchouli alcohol, Vincristine
Phytochemical	Patchouli alcohol
Drug	Vincristine
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Patchouli alcohol induces G0 /G1 cell cycle arrest and apoptosis in vincristine-resistant non-small cell lung cancer through ROS-mediated DNA damage

Pair Name	Phenethyl isothiocyanate, Dibenzoylmethane
Phytochemical	Phenethyl isothiocyanate
Drug	Dibenzoylmethane
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our results indicate that administration of DBM and PEITC in combination may be an effective strategy for inhibiting/delaying the progression of prostate cancer to androgen independence.

Pair Name	Platycodin D, Oxaliplatin
Phytochemical	Platycodin D
Drug	Oxaliplatin
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our results showed that PD is suitable as a promising agent for overcoming oxaliplatin-resistant colorectal cancer.

Pair Name	Platycodin D, Sorafenib
Phytochemical	Platycodin D
Drug	Sorafenib
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The combination of Platycodin D and sorafenib may exert potent anti-cancer effects specifically via FOXO3a

Pair Name	Platycodin D, Venetoclax
Phytochemical	Platycodin D
Drug	Venetoclax
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Platycodin D may be a potent therapeutic candidate for the treatment of AML

Pair Name	Plumbagin, Cisplatin
Phytochemical	Plumbagin
Drug	Cisplatin
Disease Info	[ICD-11: 2B62.0]	Tongue squamous cell carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	PLB combined with cisplatin is a potential therapeutic strategy against therapy TSCC cisplatin resistance.

Pair Name	Polydatin, Paclitaxel
Phytochemical	Polydatin
Drug	Paclitaxel
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Activity
Result	Polydatin may enhance the chemosensitivity of osteosarcoma cells to paclitaxel.

Pair Name	Polyphyllin I, Cisplatin
Phytochemical	Polyphyllin I
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	The results from the present study demonstrated that PPI and PPVII may function as chemosensitizers by enhancing apoptosis via the p53 pathway, reversing EMT and suppressing the CIP2A/AKT/mTOR signaling axis, and the combination with DDP may be a promising strategy for the development of new therapeutic agents.

Pair Name	Polyphyllin VI, Doxorubicin
Phytochemical	Polyphyllin VI
Drug	Doxorubicin
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Our results suggest that EEPP deserves further evaluation for development as complementary chemotherapy for colorectal cancer.

Pair Name	Pristimerin, Sorafenib
Phytochemical	Pristimerin
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Pristimerin synergistically sensitizes conditionally reprogrammed patient derived-primary hepatocellular carcinoma cells to sorafenib through endoplasmic reticulum stress and ROS generation by modulating Akt/FoxO1/p27kip1 signaling pathway

Pair Name	Pterostilbene, Fluorouracil
Phytochemical	Pterostilbene
Drug	Fluorouracil
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These results provide a rationale for novel combination treatment strategies, especially for patients with 5-FU-resistant tumors expressing ER-β protein.

Pair Name	Quercitrin, Insulin
Phytochemical	Quercitrin
Drug	Insulin
Disease Info	[ICD-11: 5A80]	Polycystic ovary syndrome		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	PM20D1 and PI3K/Akt were required for lipolysis and endocrine regulation in PCOS-IR to restore ovarian function and maintain normal endocrine metabolism. By upregulating the expression of PM20D1, quercitrin activated the PI3K/Akt signaling pathway, improved adipocyte catabolism, corrected reproductive and metabolic abnormalities, and had a therapeutic effect on PCOS-IR.

Pair Name	Resveratrol, Cisplatin
Phytochemical	Resveratrol
Drug	Cisplatin
Disease Info	[ICD-11: 2C73]	Ovarian cancer		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Resveratrol Enhances Cytotoxic Effects of Cisplatin by Inducing Cell Cycle Arrest and Apoptosis in Ovarian Adenocarcinoma SKOV-3 Cells through Activating the p38 MAPK and Suppressing AKT

Pair Name	Resveratrol, Rapamycin
Phytochemical	Resveratrol
Drug	Rapamycin
Disease Info	[ICD-11: 2D10.1]	Papillary thyroid cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The present study suggests that the combination of rapamycin and resveratrol may be a promising strategy for the treatment of papillary thyroid cancer.

Pair Name	Resveratrol, Sorafenib
Phytochemical	Resveratrol
Drug	Sorafenib
Disease Info	[ICD-11: 2C90.0]	Renal cell carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	PEGylated resveratrol combined with sorafenib can achieve synergistic anti-RCC activity, and the mechanism may be related to the inhibition of Akt/mTOR/p70S6k-4EBP-1 and c-Raf7MEK/ERK signaling pathways.

Pair Name	Resveratrol, Talazoparib
Phytochemical	Resveratrol
Drug	Talazoparib
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Resveratrol sensitizes breast cancer to PARP inhibitor, talazoparib through dual inhibition of AKT and autophagy flux

Pair Name	Retinoic acid, PI3K inhibitor
Phytochemical	All-trans-retinoic acid
Drug	PI3K inhibitor
Disease Info	[ICD-11: 2D4Y]	Adenoid cystic carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	We displayed the morphologically and genetic featured PDXs which recapitulated the heterogeneity of original ACC tumors, indicating that the models could be used as a platform for drug screening for therapy response. The feasibility of combination treatment approaches for dual targets were confirmed, providing new regimens for personalized therapies in ACC.

Pair Name	Rhein, Oxaliplatin
Phytochemical	Rhein
Drug	Oxaliplatin
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	These data demonstrate that Rhein can induce apoptosis and enhance the oxaliplatin sensitivity of PC cells, suggesting that Rhein may be an effective strategy to overcome drug resistance in the chemotherapeutic treatment of PC.

Pair Name	Rhein, Pemetrexed
Phytochemical	Rhein
Drug	Pemetrexed
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Our findings demonstrated that the potential application of rhein as a candidate drug in combination with PTX is promising for treatment of the human lung cancer.

Pair Name	Rhizoma Paridis saponins, Sorafenib
Phytochemical	Rhizoma Paridis saponins
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	All of that provided possibility to overcome the intolerance of sorafenib by drug compatibility through protection against mitochondria damage, inhibition of anaerobic glycolysis and suppression of lipid synthesis based on PI3K/Akt/mTOR pathway.

Pair Name	Saikosaponin A, Docetaxel
Phytochemical	Saikosaponin A
Drug	Docetaxel
Disease Info	[ICD-11: 2C82]	Prostate cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	SSA is posed as a novel QCCs-eradicating agent by aggravating autophagy in QCCs. In combination with the current therapy, SSA has potential to improve treatment effectiveness and to prevent cancer recurrence.

Pair Name	Saikosaponin D, 1,9-Pyrazoloanthrone
Phytochemical	Saikosaponin D
Drug	1,9-Pyrazoloanthrone
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	A dramatic inhibition of cellular proliferation, invasion, and migration in cells treated with Ssd alone or in combination with SP600125 was observed

Pair Name	Shikonin, 4-hydroxytamoxifen
Phytochemical	Shikonin
Drug	4-hydroxytamoxifen
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	The combination of SK and 4-OHT shows highly efficient anticancer effects on breast cancer therapy. SK may be a promising candidate as an adjuvant to 4-OHT for breast cancer treatments, especially for ER- breast cancer.

Pair Name	Shikonin, BEZ235
Phytochemical	Shikonin
Drug	BEZ235
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	We found that low doses shikonin and dual PI3K-mTOR inhibitor (BEZ235) have a synergistic effect that inhibits the spheroid formation from chemoresistant lung cancer sublines. Inhibiting the proliferation of lung cancer stem cells is believed to reduce the recurrence of lung cancer; therefore, shikonin's anti-drug resistance and anti-cancer stem cell activities make it a highly interesting molecule for future combined lung cancer therapy.

Pair Name	Shikonin, Doxorubicin
Phytochemical	Shikonin
Drug	Doxorubicin
Disease Info	[ICD-11: 2B33.5]	Lymphoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	These data suggest that shikonin may be an encouraging chemotherapeutic agent in the clinical treatment of BL.

Pair Name	Shikonin, Erlotinib
Phytochemical	Shikonin
Drug	Erlotinib
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These results suggest that the combination of erlotinib with shikonin or its derivatives might be a potential strategy to overcome drug resistance to erlotinib.

Pair Name	Shikonin, Temozolomide
Phytochemical	Shikonin
Drug	Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	From our results we conclude that dual treatment with SHK and TMZ may constitute a powerful new tool for GBM treatment by reducing therapy resistance and tumor recurrence.

Pair Name	Shikonin, TNF-related apoptosis inducing ligand
Phytochemical	Shikonin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The results indicated that shikonin sensitized resistant cancer cells to TRAIL-induced cytotoxicity via the modulation of the JNK, STAT3 and AKT pathways, the downregulation of antiapoptotic proteins and the upregulation of proapoptotic proteins.

Pair Name	Shogaol, Fluorouracil
Phytochemical	Shogaol
Drug	Fluorouracil
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Influence of 6-shogaol potentiated on 5-fluorouracil treatment of liver cancer by promoting apoptosis and cell cycle arrest by regulating AKT/mTOR/MRP1 signalling

Pair Name	Silibinin, Sorafenib
Phytochemical	Silibinin
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	These results suggested that silibinin improved the efficacy of sorafenib in HCC therapy, indicating a clinical promising therapeutic strategy for HCC patients.

Pair Name	Sulforaphane, Cisplatin
Phytochemical	Sulforaphane
Drug	Cisplatin
Disease Info	[ICD-11: 2C28]	Malignant mesothelioma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Pro-oxidant activity of sulforaphane and cisplatin potentiates apoptosis and simultaneously promotes autophagy in malignant mesothelioma cells

Pair Name	Sulforaphane, Everolimus
Phytochemical	Sulforaphane
Drug	Everolimus
Disease Info	[ICD-11: 2C94]	Bladder cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The addition of SFN to the long-term everolimus application inhibits resistance development in bladder cancer cells in vitro. Therefore, sulforaphane may hold potential for treating bladder carcinoma in patients with resistance to an mTOR inhibitor.

Pair Name	Sulforaphane, Everolimus
Phytochemical	Sulforaphane
Drug	Everolimus
Disease Info	[ICD-11: 2C94]	Bladder cancer		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	The addition of SFN to the long-term everolimus application inhibits resistance development in bladder cancer cells in vitro. Therefore, sulforaphane may hold potential for treating bladder carcinoma in patients with resistance to an mTOR inhibitor.

Pair Name	Sulforaphane, Gefitinib
Phytochemical	Sulforaphane
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	SFN overcame T790M-mediated gefitinib resistance in vitro through EMT. Thus, a combination of gefitinib and SFN may be a beneficial treatment strategy for lung cancer patients with acquired resistance due to T790M mutation.

Pair Name	Sulforaphane, Lapatinib
Phytochemical	Sulforaphane
Drug	Lapatinib
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Therapeutic Mechanism of Lapatinib Combined with Sulforaphane on Gastric Cancer

Pair Name	Sulforaphane, PP242
Phytochemical	Sulforaphane
Drug	PP242
Disease Info	[ICD-11: 2B70]	Esophageal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our findings demonstrate that PP242 enhances the anti-tumor activity of SFN by blocking SFN-induced activation of Akt/mTOR pathway in ESCC, which provides a rationale for treating ESCC using SFN combined with Akt/mTOR pathway inhibitors.

Pair Name	Tangeretin, Metformin
Phytochemical	Tangeretin
Drug	Metformin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The current work underscores the importance of metformin as an ERMA in tackling breast cancer and as a novel approach to boost its anticancer activity via a synergistic combination with tangeretin.

Pair Name	Tanshinone IIA, Cisplatin
Phytochemical	Tanshinone IIA
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The combination of Tan IIA and cisplatin exhibited the most significant difference. Tanshinone IIA may function as a novel option for combination therapy for non-small-cell lung cancer treatment.

Pair Name	Tanshinone IIA, Imatinib
Phytochemical	Tanshinone IIA
Drug	Imatinib
Disease Info	[ICD-11: 2A20.1]	Chronic myelogenous leukemia		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The results revealed that Tan IIA enhanced the inhibitory effect of imatinib on TIB‑152 cell proliferation, migration and invasion, and induced apoptosis, which may be associated with inhibition of the PI3K/AKT/mTOR signaling pathway.

Pair Name	Tanshinone IIA, Nutlin-3
Phytochemical	Tanshinone IIA
Drug	Nutlin-3
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	The results of this study demonstrate that the Nutlin-3 plus Tanshinone IIA combination exerts synergistic anti-leukemia effects by regulating the p53 and AKT/mTOR pathways, although further investigation is warranted. Small-molecule MDM2 antagonists plus Tanshinone IIA may thus be a promising strategy for the treatment of acute leukemia.

Pair Name	Taurine, Temozolomide
Phytochemical	Taurine
Drug	Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The study showed that the combination between TMZ and TAU has a potential in anticancer properties against U-251 MG manifested by the induction of G2/M arrest and apoptosis. These results suggest that this combination may be useful to enhance the efficacy and reduce some adverse events of GBM treatment in the future.

Pair Name	Tea polyphenol, Paclitaxel
Phytochemical	Tea polyphenol
Drug	Paclitaxel
Disease Info	[ICD-11: 2C73]	Ovarian cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our results showed that the combination of green tea and PTX could be more potent than the individual drug to induce cytotoxicity and apoptosis in ovarian cancer cells.

Pair Name	Tectorigenin, Paclitaxel
Phytochemical	Tectorigenin
Drug	Paclitaxel
Disease Info	[ICD-11: 2C73]	Ovarian cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Activity
Result	These data suggest that tectorigenin could sensitize paclitaxel-resistant human ovarian cancer cells through inactivation of the Akt/IKK/IκB/NFκB signaling pathway, and promise a new intervention to chemosensitize paclitaxel-induced cytotoxicity in ovarian cancer.

Pair Name	Tetrandrine, Sorafenib
Phytochemical	Tetrandrine
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The antitumour activity of sorafenib plus tetrandrine may be attributed to the induction of the intrinsic apoptosis pathway through ROS/Akt signaling. This finding provides a novel approach that may broaden the clinical application of sorafenib.

Pair Name	Thymoquinone, Cyclophosphamide
Phytochemical	Thymoquinone
Drug	Cyclophosphamide
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The current findings suggested that TQ can alter the cell cycle progression and induce cell death independent of FASN mediated signaling. In terms of clinical perspective, the present study clearly showed that TQ can broadly augment the effect of cyclo in breast cancer cases irrespective of Her-2+ or Her-.

Pair Name	Tubeimoside I, Temozolomide
Phytochemical	Tubeimoside I
Drug	Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	We first demonstrated that synergistic effects of TBMS1 and TMZ induced apoptosis in GBM cells through reducing MGMT expression and inhibiting the EGFR induced PI3K/Akt/mTOR/NF-κB signaling pathway. This study provides a rationale for combined application of TMZ and TBMS1 as a potential chemotherapeutic treatment for MGMT+ GBM patients.

Pair Name	Ursolic acid, Doxorubicin
Phytochemical	Ursolic acid
Drug	Doxorubicin
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	UA may be a novel anticancer strategy and could be considered for investigation as a complementary chemotherapy agent in the future.

Pair Name	Ursolic acid, Epirubicin
Phytochemical	Ursolic acid
Drug	Epirubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	These findings indicate that UA can dramatically enhance the sensitivity of MCF-7 and MDA-MB-231 cells to EPI by modulating the autophagy pathway. Our study may provide a new therapeutic strategy for combination therapy.

Pair Name	Vitamin C, Cimetidine
Phytochemical	Vitamin C
Drug	Cimetidine
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	We concluded that the synergistic combination provided a promising anti-neoplastic effect via reducing the angiogenesis, oxidative stress, increasing apoptosis,as well as inhibiting the activation of PI3K/AKT/mTOR cue, and suggesting its use as a treatment option for breast cancer.

Pair Name	Zerumbone, Gefitinib
Phytochemical	Zerumbone
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our study suggested that zerumbone combined with gefitinib could effectively inhibit lung cancer for multi-model therapies, including the inhibition of tumor growth, angiogenesis, induce cell apoptosis, and ferroptosis.

Pair Name	Zeylenone, Cisplatin
Phytochemical	Zeylenone
Drug	Cisplatin
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Zeylenone synergizes with cisplatin in osteosarcoma by enhancing DNA damage, apoptosis, and necrosis via the Hsp90/AKT/GSK3β and Fanconi anaemia pathway

Pair Name	Andrographolide, Fluorouracil
Phytochemical	Andrographolide
Drug	Fluorouracil
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our data provide novel evidence for andrographis-mediated reversal of 5FU resistance, highlighting its potential role as an adjunct to conventional chemotherapy in CRC.

Pair Name	Beta-Elemene, Oxaliplatin
Phytochemical	Beta-Elemene
Drug	Oxaliplatin
Disease Info	[ICD-11: 2B91]	Colorectal cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our findings show that β-elemene can block the reduction of CTR1 resulting from oxaliplatin treatment, and therefore has a synergistic anti-HCC effect with oxaliplatin by enhancing cellular uptake of oxaliplatin. The synergistic effects of β-elemene and oxaliplatin deserve further evaluation in clinical settings.

Pair Name	Bufalin, Cisplatin
Phytochemical	Bufalin
Drug	Cisplatin
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	It was demonstrated that bufalin reversed acquired cisplatin resistance and significantly induced apoptosis through the AKT pathway. These results imply that bufalin could extend the therapeutic effect of cisplatin on GC cells when administered in combination.

Pair Name	Caffeic acid phenethyl ester, Doxorubicin
Phytochemical	Caffeic acid phenethyl ester
Drug	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our results suggest that CAPE treatment reversed DOX resistance in breast cancer cells, at least in part by inhibiting Akt/mTOR/SREBP1 pathway-mediated lipid metabolism, indicating that CAPE may be an effective substance to assist in the treatment of breast cancer.

Pair Name	Chrysin, Fluorouracil
Phytochemical	Chrysin
Drug	Fluorouracil
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Potentiating activities of chrysin in the therapeutic efficacy of 5-fluorouracil in gastric cancer cells

Pair Name	Cordycepin, Cisplatin
Phytochemical	Cordycepin
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Our results suggested that Cor in combination with DDP could be an additional therapeutic option for the treatment of DDP-resistant NSCLC.

Pair Name	Curcumin, Lenvatinib
Phytochemical	Curcumin
Drug	Lenvatinib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	We report that Curcumin reverses Lenvatinib resistance in HCC, and that their combination has clinical application potential for adjunctive treatment in HCC.

Pair Name	Demethoxycurcumin, AT101
Phytochemical	Demethoxycurcumin
Drug	AT101
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Regulate Info	Up-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Combined treatment with different drugs might be an option to efficiently overcome chemoresistance of GBM cells in a long-term treatment strategy.

Pair Name	Epigallocatechin gallate, Osimertinib
Phytochemical	Epigallocatechin gallate
Drug	Osimertinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	The combined use of EGFR-TKIs and EGCG significantly reversed the Warburg effect by suppressing glycolysis while boosting mitochondrial respiration, which was accompanied by increased cellular ROS and decreased lactate secretion. The combination effectively activated the AMPK pathway while inhibited both ERK/MAPK and AKT/mTOR pathways, leading to cell cycle arrest and apoptosis, particularly in drug-resistant NSCLC cells. The in vivo results obtained from mouse tumor xenograft model confirmed that EGCG effectively overcame osimertinib resistance.

Pair Name	Gambogic Acid, Gefitinib
Phytochemical	Gambogic Acid
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Gefitinib in combination with GA resulted in antitumor growth in the EGFR-T790M secondary mutation NCI-H1975 tumor model due to an enhanced apoptotic effect. This novel therapeutic strategy may be a practical approach for the treatment of patients who show gefitinib resistance.

Pair Name	Luteolin, Osimertinib
Phytochemical	Luteolin
Drug	Osimertinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Luteolin can synergize with osimertinib to overcome MET amplification and overactivation-induced acquired resistance to osimertinib by suppressing the HGF-MET-Akt pathway, suggesting the clinical potential of combining luteolin with osimertinib in NSCLC patients with acquired resistance.

Pair Name	Oleanolic Acid, Cisplatin
Phytochemical	Oleanolic Acid
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	OLO-2 treatment also exhibited up to 4.6-fold selectivity against human lung adenocarcinoma cells. Taken together, the results of the present study shed light on the drug resistance-reversing effects of OLO-2 in lung cancer cells.

Pair Name	Oleanolic Acid, Cisplatin
Phytochemical	Oleanolic Acid
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	OLO-2 treatment also exhibited up to 4.6-fold selectivity against human lung adenocarcinoma cells. Taken together, the results of the present study shed light on the drug resistance-reversing effects of OLO-2 in lung cancer cells.

Pair Name	Quercetin, Docetaxel
Phytochemical	Quercetin
Drug	Docetaxel
Disease Info	[ICD-11: 2E02]	Metastatic prostate cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways

Pair Name	Sclareol, Cisplatin
Phytochemical	Sclareol
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Sclareol has potential as an adjuvant for the treatment in NSCLC patients with cisplatin resistance.

Pair Name	Scutellarin, Cisplatin
Phytochemical	Scutellarin
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	This study identifies the unique role of scutellarin in reversing cisplatin resistance through apoptosis and autophagy, and suggests that combined cisplatin and scutellarin might be a novel therapeutic strategy for patients with NSCLC.

Pair Name	Shikonin, Gefitinib
Phytochemical	Shikonin
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Shikonin-induced cell apoptosis is closely associated with ROS elevation in the cells. These findings indicate that Shikonin can be an effective small molecule treating gefitinib-resistant NSCLC.

Pair Name	Tanshinone I, Epirubicin
Phytochemical	Tanshinone I
Drug	Epirubicin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Expression
Result	Our results suggested that Tan I could effectively improve the anti-tumor effect of EADM, and synergize EADM to reverse HIF-1α mediated resistance via targeting PI3K/AKT/HIF-1α signaling pathway.

Pair Name	Vinpocetine, Sorafenib
Phytochemical	Vinpocetine
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Regulate Info	Down-regulation	RAC-alpha serine/threonine-protein kinase		Phosphorylation
Result	Vinpocetine may be a potential candidate for sorafenib sensitization and HCC treatment, and our results may help to elucidate more effective therapeutic options for HCC patients with sorafenib resistance.