Therapeutics: c-Met receptor tyrosine kinase

Patient sample, cell culture and mouse studies suggest c-Met receptor tyrosine kinase inhibitors could help treat gastrointestinal stromal tumors (GISTs), including those resistant to imatinib. In GIST samples from patients, c-Met was activated in 20 of 36 (56%) tumors, including 9 of 14 (67%) imatinib-resistant tumors. In human GIST cell lines and mice with GIST xenografts, imatinib increased tumor cell levels of activated c-Met compared with vehicle. In GIST cell lines, imatinib plus c-Met knockdown, crizotinib or cabozantinib decreased viability compared with vehicle. In mice with GIST xenograft tumors, imatinib plus crizotinib decreased tumor growth compared with either agent alone and cabozantinib decreased tumor growth compared with imatinib. Next steps could include testing c-Met inhibitors in patients with GISTs.

Novartis AG markets Gleevec imatinib, a BCR-ABL tyrosine kinase inhibitor, to treat GISTs, chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), myeloproliferative disorder and hematologic malignancies, and has the compound in registration to treat hypertension and Phase II testing to treat melanoma and scleroderma...