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Ataxia telangiectasia mutated (ATM); DNA-dependent protein kinase (DNA-PK)

Mouse and cell culture studies suggest inhibiting the DNA-PK catalytic subunit could help treat ATM-deficient cancers. In ATM-deficient human lung cancer cell lines, small hairpin RNA-mediated knockdown of the DNA-PK catalytic subunit decreased growth compared with no knockdown. In a mouse model for non-Hodgkin's lymphoma (NHL), shRNA-mediated knockdown of Atm plus a small molecule inhibitor of the DNA-PK catalytic subunit increased survival compared with no treatment.
Celgene Corp.'s CC-115, a dual inhibitor of DNA-PK and mammalian target of rapamycin (mTOR; FRAP; RAFT1), is in Phase I testing to treat multiple myeloma, NHL and solid tumors.

SciBX 6(28); doi:10.1038/scibx.2013.714
Published online July 25, 2013

Patent application filed covering use in NHL; unavailable for licensing

Riabinska, A. et al. Sci. Transl. Med.; published online June 12, 2013;
Contact: Hans Christian Reinhardt, University Hospital of Cologne, Cologne, Germany
Contact: Shuhua Chen, same affiliation as above