ganetespib + alisertib

**Ganetespib + alisertib** is an investigational combination therapy pairing ganetespib, a second-generation small-molecule inhibitor of heat shock protein 90 (HSP90), with alisertib (MLN8237), a selective small-molecule inhibitor of Aurora kinase A (AURKA). Ganetespib disrupts HSP90 chaperone function, leading to proteasomal degradation of client proteins such as EGFR, HER2, and other oncogenic drivers, thereby inhibiting multiple signaling pathways including EGFR cascades, inducing G2/M cell-cycle arrest, and promoting apoptosis in cancer cells. Alisertib binds Aurora A kinase to impair mitotic spindle assembly, causing mitotic arrest and cell death, particularly in rapidly dividing tumor cells. This combination has been evaluated preclinically in gastric cancer (GC) models where individual agents showed limited efficacy (alisertib leaving 50–90% cells viable), but together they target complementary oncogene and tumor suppressor pathways via HSP90 and Aurora A inhibition, potentially overcoming resistance in solid tumors like GC, ovarian cancer, and breast cancer; no specific clinical trials for this exact pairing are reported, though both drugs have advanced separately in oncology trials by developers like Synta Pharmaceuticals (ganetespib) and Takeda/Millennium (alisertib).[1][7]