imatinib

Imatinib is an oral targeted cancer therapy classified as a tyrosine kinase inhibitor. It selectively inhibits the BCR-ABL fusion protein, the common driver of chronic myeloid leukemia (CML), and also blocks other kinases such as KIT and PDGFR-α/β, which are involved in certain solid tumors and hematologic diseases.

Clinical uses include chronic myeloid leukemia in chronic, accelerated, or blast phases; Philadelphia chromosome–positive acute lymphoblastic leukemia; unresectable or metastatic gastrointestinal stromal tumors; dermatofibrosarcoma protuberans; and various myeloid or lymphoid neoplasms driven by PDGFR or KIT signaling. Dosing is tailored to the indication and patient tolerance, with a typical starting dose for CML around 400 mg once daily; higher doses may be used for some other indications or in response-based adjustments.

Mechanism of action involves binding to the adenosine triphosphate (ATP) binding site of the targeted kinases, preventing phosphorylation and downstream signaling necessary for tumor cell proliferation and survival. This can lead to reduced leukemic cell growth and increased apoptosis in sensitive cells.

Pharmacokinetics and interactions: imatinib is administered orally, with absorption influenced by food; it is metabolized in the liver primarily by CYP3A4 and is excreted in feces and, to a lesser extent, urine. Drug interactions with CYP3A4 inhibitors or inducers can alter plasma levels. Monitoring of blood counts and liver function is recommended, and dose adjustments may be needed for toxicity or organ impairment.

Adverse effects commonly include edema, nausea, abdominal pain, muscle cramps, rash, and fatigue. Cytopenias, hepatotoxicity, and, less frequently, cardiac effects such as heart failure or reduced left ventricular function can occur. It is teratogenic and should be used during pregnancy only if clearly indicated. Resistance may develop via BCR-ABL mutations; responses are monitored by molecular and cytogenetic analyses, with alternative TKIs considered if resistance or intolerance arises.