This week in therapeutics




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Colorectal cancer (CRC)

B cell lymphoma 2
(BCL-2; BCL2); Bcl-xL; mammalian target of rapamycin complex 1 (mTORC1); mTORC2

Cell culture and mouse studies suggest antagonizing mTORC1 or mTORC2 in combination with BCL-2 and Bcl-xL could be useful for treating K-Ras (KRAS)- or BRAF-mutant CRC. In cell culture and two mouse models of CRC, a combination of the BCL-2 and Bcl-xL inhibitor navitoclax (ABT-263) and a pan-mTOR (FRAP; RAFT1) inhibitor decreased growth of KRAS- and BRAF-mutant tumors but not that of tumors with wild-type KRAS or BRAF. Next steps could include preclinical optimization of a combination therapy with agents in clinical development.
AbbVie Inc.'s ABT-263 is in Phase I/II testing for advanced small cell lung cancer (SCLC).
At least a dozen BCL-2 and Bcl-xL inhibitors are in Phase II or earlier development for various cancers.

SciBX 6(47); doi:10.1038/scibx.2013.1343
Published online Dec. 12, 2013

Patent and licensing status undisclosed

Faber, A.C. et al. Cancer Discov.; published online Oct. 25, 2013;
Contact: Jeffrey A. Engelman, Massachusetts General Hospital Cancer Center, Boston, Mass.