Imatinib: mechanism and primary indication.

• A. BCR-ABL tyrosine kinase inhibitor; used for CML (and BCR-ABL+ ALL)
• B. EGFR inhibitor; used for lung cancer
• C. VEGF inhibitor; used for RCC
• D. PD-1 inhibitor; used for melanoma

Answer: (A)

Imatinib works by specifically inhibiting the BCR-ABL tyrosine kinase produced by the Philadelphia chromosome. This fusion kinase is constitutively active and drives unchecked leukemic cell proliferation. Imatinib binds to the ATP-binding site of BCR-ABL, blocking phosphorylation and downstream signaling, which slows or stops the growth of the leukemic cells and promotes their death. Because the BCR-ABL fusion is the defining driver in most cases, the main indication is chronic myeloid leukemia. It also treats BCR-ABL–positive acute lymphoblastic leukemia. Imatinib can affect other kinases like c-KIT and PDGFR, which explains its use in conditions such as GI stromal tumors, but the primary and most characteristic indication remains CML. Other drugs target different pathways (eg, EGFR inhibitors for certain lung cancers, VEGF inhibitors for RCC, PD-1 inhibitors for melanoma).