Drug Information

Drug (ID: DG00651) and It's Reported Resistant Information

• Name: Bevacizumab
• Indication:
  In total 7 Indication(s)
  Brain metastases [ICD-11: 2D50-2E2Z]; Approved; [1]
  Colorectal cancer [ICD-11: 2B91]; Approved; [1]
  Lung cancer [ICD-11: 2C25]; Approved; [1]
  Metastatic colorectal cancer [ICD-11: 2D85]; Approved; [1]
  Metastatic colorectal cancer [ICD-11: 2D85]; Approved; [1]
  Ovarian cancer [ICD-11: 2C73]; Approved; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Retinal disorders [ICD-11: 9B78]; [2]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Ovarian cancer [ICD-11: 2C73]; [1]
• Target: Vascular endothelial growth factor A (VEGFA); VEGFA_HUMAN; [1]
• TTD Drug ID: D04KBL

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [3]

• Molecule Alteration: Missense mutation; p.R132S (c.394C>A)
• Sensitive Disease: Brain glioma [ICD-11: 2A00.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Brain; N.A.
• Mechanism Description: The missense mutation p.R132S (c.394C>A) in gene IDH1 cause the sensitivity of Bevacizumab by aberration of the drug's therapeutic target

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [3]

• Molecule Alteration: Missense mutation; p.R132C (c.394C>T)
• Sensitive Disease: Brain glioma [ICD-11: 2A00.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Brain; N.A.
• Mechanism Description: The missense mutation p.R132C (c.394C>T) in gene IDH1 cause the sensitivity of Bevacizumab by aberration of the drug's therapeutic target

Key Molecule: Oxalosuccinate decarboxylase (IDH1) [3]

• Molecule Alteration: Missense mutation; p.R132L (c.395G>T)
• Sensitive Disease: Brain glioma [ICD-11: 2A00.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Brain; N.A.
• Mechanism Description: The missense mutation p.R132L (c.395G>T) in gene IDH1 cause the sensitivity of Bevacizumab by aberration of the drug's therapeutic target

Ovarian cancer [ICD-11: 2C73]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: EPH receptor B4 (EPHB4) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Primary pulmonary lymphoepithelioma-like carcinoma tissue; N.A.
• In Vivo Model: Athymic BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Mechanism Description: EphB4 was overexpressed in BV-resistant xenograft models instead of other common receptor tyrosine kinases. In addition, when coadministrated with EphB4 blocker NVP-BHG712, the antitumor effect of BV was significantly enhanced in the resistant model, further confirmed the role of EphB4 in BV-resistant ovarian cancer. These results indicate that NVP-BHG712 reverses EphB4 overexpression-mediated resistance to BV.

References

• Ref 1: Resistance to bevacizumab in ovarian cancer SKOV3 xenograft due to EphB4 overexpression .J Cancer Res Ther. 2019 Oct-Dec;15(6):1282-1287. doi: 10.4103/0973-1482.204896. 10.4103/0973-1482.204896
• Ref 2: Anti-VEGF-refractory exudative age-related macular degeneration: differential response according to features on optical coherence tomography .Korean J Ophthalmol. 2013 Dec;27(6):425-32. doi: 10.3341/kjo.2013.27.6.425. Epub 2013 Nov 15. 10.3341/kjo.2013.27.6.425
• Ref 3: Correlation between IDH1 gene mutation status and survival of patients treated for recurrent gliomaAnticancer Res. 2011 Dec;31(12):4457-63.