Therapeutics: v-abl Abelson murine leukemia viral oncogene homolog 1 (ABL1); heat shock protein 90 (Hsp90)

In vitro studies suggest inhibiting ABL1 could help sensitize tumors to Hsp90 inhibitors. In a human prostate cancer cell line, a tool compound inhibitor of ABL1 plus the Hsp90 inhibitor ganetespib increased apoptosis compared with ganetespib alone. In patient-derived renal cell carcinoma (RCC) tumor samples treated with ganetespib or other Hsp90 inhibitors, pretreatment with the ABL1 inhibitor increased tumor cell uptake of the Hsp90 inhibitor compared with no pretreatment. Next steps could include testing the combination of ABL1 and Hsp90 inhibitors in animal models of cancer.

Synta Pharmaceuticals Corp. has ganetespib (STA-9090) in Phase III testing to treat acute myelogenous leukemia (AML) and other cancers. ...