Details of the Drug Combination

General Information of Drug Combination (ID: DCSEFCM)

• Drug Combination Name: Erlotinib + Bevacizumab
• Indication: Metastatic colorectal cancer; Non-small-cell lung cancer; Hypopharyngeal squamous cell carcinoma; Hepatocellular carcinoma; Status: Phase 1 [1]
• Component Drugs:
  Erlotinib (DMCMBHA): Small molecular drug
  Bevacizumab (DMSD1UN): Monoclonal antibody

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Erlotinib

Disease Entry	ICD 11	Status	REF
Adrenal gland neoplasm	N.A.	Approved	[2]
Adult hepatocellular carcinoma	N.A.	Approved	[2]
Brain cancer	2A00	Approved	[2]
Esophageal disorder	N.A.	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Non-small-cell lung cancer	2C25.Y	Approved	[3]
Pancreatic adenocarcinoma	N.A.	Approved	[2]
Psoriasis	EA90	Approved	[2]
Salivary gland squamous cell carcinoma	N.A.	Approved	[2]
Pancreatic cancer	2C10	Phase 3	[3]
Colon cancer	2B90.Z	Phase 2	[3]
Ependymoma	2A00.0Y	Investigative	[2]
Neoplastic meningitis	N.A.	Investigative	[2]
Neuroblastoma	2D11.2	Investigative	[2]

Erlotinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[29]

Erlotinib Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[30]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[31]

Erlotinib Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[32]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[33]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[33]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[33]

Erlotinib Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Increases Response	[34]

Indication(s) of Bevacizumab

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[4]
Adult acute monocytic leukemia	N.A.	Approved	[5]
Biliary tract cancer	2C17	Approved	[6]
Childhood acute megakaryoblastic leukemia	N.A.	Approved	[5]
Cholangiocarcinoma	2C12.10	Approved	[7]
Colon adenocarcinoma	N.A.	Approved	[8]
Colorectal carcinoma	N.A.	Approved	[9]
Esophageal disorder	N.A.	Approved	[10]
Glioblastoma	2A00	Approved	[11]
Glioblastoma of brain	2A00.00	Approved	[12]
Hemangioblastoma	N.A.	Approved	[13]
Intracranial meningioma	N.A.	Approved	[14]
Lung adenocarcinoma	N.A.	Approved	[15]
Malignant epithelial tumor of ovary	N.A.	Approved	[16]
Metastatic colorectal cancer	2B91	Approved	[17]
Non-small-cell lung cancer	2C25.Y	Approved	[18]
Rectal adenocarcinoma	2B92	Approved	[19]
Von hippel-lindau disease	5A75	Approved	[20]
Colorectal cancer	2B91.Z	Phase 3	[21]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2/3	[22]
Brain metastases	2D50	Phase 2	[21]
Lung cancer	2C25.0	Phase 1	[21]
Solid tumour/cancer	2A00-2F9Z	Phase 1	[23]
Ovarian cancer	2C73	Application submitted	[23]
Adult glioblastoma	N.A.	Investigative	[24]
Colon cancer	2B90.Z	Investigative	[25]
Fallopian tube cancer	2C74	Investigative	[26]
Hereditary hemorrhagic telangiectasia	LA90.00	Investigative	[27]
Lung large cell carcinoma	N.A.	Investigative	[28]

Bevacizumab Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Vascular endothelial growth factor A (VEGFA)	TTOHSBA	VEGFA_HUMAN	Inhibitor	[35]
HUMAN vascular endothelial growth factor (VEGF)	TT140V6	VEGFA_HUMAN; VEGFB_HUMAN; VEGFC_HUMAN; VEGFD_HUMAN	Inhibitor	[22]

Bevacizumab Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Mastermind-like protein 2 (MAML2)	OT1TSVAR	MAML2_HUMAN	Increases ADR	[36]
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3)	OT25JBA3	F263_HUMAN	Increases ADR	[36]
TGF-beta receptor type-2 (TGFBR2)	OT3P7GZP	TGFR2_HUMAN	Increases ADR	[36]
Beta-parvin (PARVB)	OT9OGVWX	PARVB_HUMAN	Increases ADR	[36]
Mitochondrial peptide methionine sulfoxide reductase (MSRA)	OTBS15SD	MSRA_HUMAN	Increases ADR	[36]
Synaptic vesicle glycoprotein 2C (SV2C)	OTIH108W	SV2C_HUMAN	Increases ADR	[36]

References

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• [2] Erlotinib FDA Label
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• [22] ClinicalTrials.gov (NCT04275414) Bevacizumab in Severe or Critical Patients With COVID-19 Pneumonia (BEST-CP)
• [23] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
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• [25] Colon cancer. Crit Rev Oncol Hematol. 2010 May;74(2):106-33.
• [26] OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45.
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• [33] Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706.
• [34] Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39. doi: 10.1056/NEJMoa040938. Epub 2004 Apr 29.
• [35] FDA Approved Drug Products from FDA Official Website. 2004. Application Number: (ANDA) 125085.
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