tyrosinekinaseremmers

Tyrosine kinase inhibitors, also known as tyrosinekinaseremmers in Dutch, are a class of targeted cancer drugs that block the enzymatic activity of tyrosine kinases, enzymes that propagate signaling for cell growth and survival. Most TKIs are small molecules that compete with ATP for binding to the kinase, or bind at other sites to prevent phosphorylation of tyrosine residues.

TKIs are used to treat cancers driven by abnormal tyrosine kinase activity. Notable examples include chronic myeloid leukemia (BCR-ABL), non-small cell lung cancer with activating EGFR mutations, and ALK-rearranged lung cancer. They are also employed against tumors dependent on VEGFR, MET, RET, ROS1, KIT and other kinases. TKIs can be highly selective for a single kinase or inhibit multiple targets.

Clinical development has progressed through generations. First-generation inhibitors can be highly effective but may lose activity due to resistance mutations; later generations were designed to overcome common resistance mechanisms and, in some cases, to improve central nervous system penetration. Representative examples include imatinib (BCR-ABL, KIT), dasatinib and nilotinib (BCR-ABL and others), gefitinib and erlotinib (EGFR), and osimertinib (EGFR T790M). ALK inhibitors include crizotinib, ceritinib, alectinib, brigatinib and lorlatinib.

Common adverse effects vary by drug but often include rash, diarrhea, fatigue, hypertension, and elevated liver enzymes. Thrombocytopenia or anemia, edema, and rare cardiotoxicity can occur. Resistance may arise through kinase mutations, gene amplification, or activation of alternative signaling pathways. TKIs are typically taken orally and require molecular testing to identify actionable mutations before use.