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c-Myc (MYC); mammalian target of rapamycin (mTOR; FRAP; RAFT1); 3-phosphoinositide dependent protein kinase-1 (PDPK1); polo-like kinase 1 (PLK1; STPK13)

Cell culture and mouse studies suggest combining PLK1 and mTOR inhibitors could help treat MYC-driven cancers. In cultured cells, PLK1 coimmunoprecipitated and phosphorylated MYC in a PDPK1-dependent manner. In a mouse xenograft model of colorectal cancer, the mTOR inhibitor BEZ235 plus a PLK1 inhibitor decreased MYC expression and tumor growth compared with vehicle or either inhibitor alone. Next steps could include combining PLK1 inhibitors with mTOR and PI3K inhibitors.
BEZ235, a dual inhibitor of PI3K and mTOR from Novartis AG, is in Phase I/II testing to treat cancer.
At least nine companies have PLK1 inhibitors in Phase III testing or earlier to treat cancer.

SciBX 6(34); doi:10.1038/scibx.2013.919
Published online Sept. 5, 2013

Patent application filed; available for licensing

Tan, J. et al. Cancer Discov.;
published online July 25, 2013;
Contact: Qiang Yu, Genome Institute of Singapore, Singapore