As an inhibitor of heat shock protein 90 (Hsp90), the drug ganetespib represents a new treatment opportunity for persons with non-small cell lung cancer (NSCLC) that is positive for the cancer-driving protein anaplastic lymphoma kinase (ALK). Ganetespib also may be effective in patients who have developed resistance to crizotinib, the only FDA-approved targeted therapy for this disease.
EML4–ALK gene rearrangements define a unique subset of patients with NSCLC, explained David A. Proia, PhD, and colleagues in Cancer Discovery, a journal of the American Association for Cancer Research (AACR). Proia is the associate director of cancer biology at Synta Pharmaceuticals Corporation in Lexington, Massachusetts; Synta developed ganetespib and funded this study.
Hsp90 ensures the proper function of many different proteins, including ALK, noted an AACR statement announcing the research findings. When Hsp90 is blocked, ALK cannot function properly, and the cell destroys it. The loss of ALK triggers death of the cancer cells, causing tumors to shrink.
Not only did ganetespib prove to be 30 times more potent than crizotinib against a cultured ALK-positive NSCLC cell line, resulting in the complete loss of ALK protein expression, but the drug also was active against ALK-positive NSCLC cell lines that had become resistant to crizotinib.