crizotinib + onalespib

Crizotinib + onalespib is an investigational combination therapy evaluated primarily in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Crizotinib is a small molecule tyrosine kinase inhibitor targeting ALK, ROS1, c-MET, and RON kinases. It inhibits tumor cell proliferation by blocking phosphorylation of these kinases, which are often aberrantly activated in certain cancers[4]. Onalespib (AT13387) is a small molecule inhibitor of heat shock protein 90 (HSP90), a molecular chaperone essential for the stability and function of multiple client proteins including ALK. By inhibiting HSP90, onalespib disrupts the maturation and stability of oncogenic proteins such as ALK[1][6]. Preclinical studies suggested that combining these agents could delay resistance to crizotinib by targeting both the driver kinase and its chaperone; however, clinical trials have shown that while this combination can be safely administered with some activity observed, it did not significantly improve progression-free survival compared to crizotinib alone in ALK-positive NSCLC patients[1][5][7].

Brand names

None known for the combination

Other names

crizotinib and onalespibCZT + onalespib