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Chronic lymphocytic leukemia (CLL)

RAD51 homolog (RAD51); activation-induced cytidine deaminase (AICDA; AID)

Studies in patient-derived cells and in mice suggest antagonizing RAD51 could be useful for treating AID-expressing CLL. AID and RAD51 are enzymes involved in DNA repair. In a panel of samples from 74 patients with CLL, about 40% of tumors had higher AID expression than nontumor tissue. In cultured human CLL tumors with elevated AID levels, a RAD51 inhibitor decreased tumor growth and increased sensitivity to ionizing radiation compared with vehicle. Next steps include preclinical development of new chemical entities derived from the RAD51 inhibitor used in the study.
Cyteir Therapeutics Inc.'s RAD51 inhibitor, C1523, is in preclinical development for AID+ CLL and other AID-overexpressing malignancies.

SciBX 6(22); doi:10.1038/scibx.2013.544
Published online June 6, 2013

Patent pending; licensed to Cyteir Therapeutics

Lamont, K.R. et al. J. Exp. Med.; published online April 15, 2013;
Contact: Kevin D. Mills, The Jackson Laboratory, Bar Harbor, Maine