RTKinhibiitorid

RTKinhibiitorid, or receptor tyrosine kinase inhibitors, are a class of targeted cancer therapies that block signaling through receptor tyrosine kinases (RTKs), proteins on the cell surface that regulate growth, survival, and angiogenesis. They include small-molecule tyrosine kinase inhibitors (TKIs) that inhibit the kinase activity inside the receptor, and monoclonal antibodies that prevent ligand binding or receptor activation.

TKIs typically compete with ATP for binding to the kinase domain, reducing phosphorylation and downstream signaling in pathways such as RAS/RAF/MEK/ERK and PI3K/AKT/mTOR. Some inhibitors are irreversible or multi-target, affecting several RTKs at once. Examples of targeted RTKs include EGFR, ALK, ROS1, MET, RET, NTRK, VEGFR, PDGFR, KIT, and FGFR. Clinically used agents include EGFR inhibitors like gefitinib and erlotinib (with newer agents such as osimertinib), ALK/ROS1 inhibitors like crizotinib, ceritinib, and alectinib, NTRK inhibitors larotrectinib and entrectinib, and multi-target VEGFR inhibitors such as sorafenib, sunitinib, pazopanib, and lenvatinib. Inhibition of MET, RET, and other RTKs is addressed by newer agents like capmatinib, tepotinib, selpercatinib, and pralsetinib.

RTK inhibitors have transformed treatment for several cancers, notably cancers with actionable RTK alterations, including EGFR-mutant and ALK-rearranged non-small cell lung cancer and tumors with NTRK fusions. Resistance frequently develops through secondary mutations in the kinase domain, bypass signaling, or histologic changes, necessitating combination strategies or sequential therapy. Common adverse effects include rash, diarrhea, hypertension, hepatotoxicity, and QT prolongation, with management guided by treatment type and patient factors.