Drug Information

Drug (ID: DG00344) and It's Reported Resistant Information

• Name: Pembrolizumab
• Indication:
  In total 11 Indication(s)
  Melanoma [ICD-11: 2C30]; Approved; [1]
  Diffuse large B-cell lymphoma [ICD-11: 2A81]; Application submitted; [1]
  Breast cancer [ICD-11: 2C60]; Phase 3; [1]
  Colorectal cancer [ICD-11: 2B91]; Phase 3; [1]
  Esophageal cancer [ICD-11: 2B70]; Phase 3; [1]
  Liver cancer [ICD-11: 2C12]; Phase 3; [1]
  Lung cancer [ICD-11: 2C25]; Phase 3; [1]
  Renal cell carcinoma [ICD-11: 2C90]; Phase 3; [1]
  Ovarian cancer [ICD-11: 2C73]; Phase 2; [1]
  Prostate cancer [ICD-11: 2C82]; Phase 2; [1]
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Melanoma [ICD-11: 2C30]; [1]
• Target: Programmed cell death protein 1 (PD-1); PDCD1_HUMAN; [1]
• TTD Drug ID: D08ANZ
• DrugBank ID: DB09037

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

Melanoma [ICD-11: 2C30]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Nras (NRAS) [1]

• Molecule Alteration: Missense mutation; p.Q61R
• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Circulating tumour DNA (ctDNA) analysis; Whole genome plasma DNA sequencing assay
• Experiment for Drug Resistance: Computer tomography (CT) assay; Positron emission tomography assay
• Mechanism Description: Mutations in NRAS have been found in 8-26% of patients with acquired resistance to BRAF inhibitors. We analysed the presence of NRASQ61k and NRASQ61R in the ctDNA extracted from 7 melanoma patients with progressive disease who had previously responded to treatment with vemurafenib (n = 2) or dabrafenib/trametinib (n = 5). Two samples were positive for NRASQ61k and one sample had an NRASQ61R mutation, all three were derived from patients treated with dabrafenib/trametinib.

References

• Ref 1: Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma. Oncotarget. 2015 Dec 8;6(39):42008-18. doi: 10.18632/oncotarget.5788.