Imatinib (Gleevec) revolutionised CML treatment by inhibiting which molecular target?
- A BCR-ABL tyrosine kinase (the constitutively active fusion protein resulting from the Philadelphia chromosome t(9;22) translocation) ✓
- B BCL-2 anti-apoptotic protein in CLL cells
- C EGFR (HER1) tyrosine kinase in NSCLC
- D ALK kinase rearrangements in lung cancer
Correct answer: A. BCR-ABL tyrosine kinase (the constitutively active fusion protein resulting from the Philadelphia chromosome t(9;22) translocation)
Explanation
Imatinib is a small-molecule tyrosine kinase inhibitor that competitively inhibits BCR-ABL, the constitutively active tyrosine kinase encoded by the Philadelphia chromosome translocation t(9;22)(q34;q11.2) in CML. It also inhibits c-KIT (GIST) and PDGFR. BCL-2 is targeted by venetoclax in CLL; EGFR by erlotinib/gefitinib in NSCLC; ALK by crizotinib/alectinib. Imatinib transformed CML from a disease with median survival of 3–5 years into one with near-normal life expectancy.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.