Kinaseinhibitors

Kinase inhibitors are a class of therapeutic agents that suppress the enzymatic activity of kinases, enzymes that add phosphate groups to substrates and regulate signaling pathways involved in cell growth, survival, and differentiation. Most kinase inhibitors are small molecules that compete with ATP at the kinase active site, but others are allosteric inhibitors that bind outside the catalytic site or covalent inhibitors that form a durable bond with the enzyme. By blocking signaling cascades mediated by receptor tyrosine kinases or cytoplasmic kinases, these drugs can slow or halt the proliferation of cancer cells or modulate immune responses.

Kinase inhibitors are typically classified by their targets: receptor tyrosine kinases (for example, EGFR, VEGFR, HER2), non-receptor tyrosine kinases (such as BCR-ABL, Src), and serine/threonine kinases (such as AKT, MEK). Many agents are ATP-competitive, binding to the ATP-binding pocket; others are allosteric or covalent inhibitors. Notable examples include imatinib, dasatinib, and nilotinib (BCR-ABL inhibitors) used in chronic myeloid leukemia; gefitinib and erlotinib (EGFR inhibitors) for certain lung cancers; sorafenib and sunitinib (multi-target TKIs) used in various cancers; vemurafenib (BRAF inhibitor) for melanoma.

Clinical use hinges on the molecular profile of the tumor and can yield rapid responses in some patients, but resistance often develops through mutations in the target kinase, activation of alternative pathways, or pharmacokinetic factors. Side effects vary but commonly include skin rash, diarrhea, hypertension, liver enzyme elevations, and cytopenias. Safety and efficacy require biomarker-guided patient selection, careful monitoring, and sometimes combination strategies to overcome resistance.