Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Cancer+Discov 2017 ; 7 (1): 20-37 Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Targeting DNA Repair in Cancer: Beyond PARP Inhibitors #MMPMID28003236
Brown JS; O?Carrigan B; Jackson SP; Yap TA
Cancer Discov 2017[Jan]; 7 (1): 20-37 PMID28003236show ga
Germline aberrations in critical DNA repair and DNA-damage response (DDR) genes cause cancer predisposition, while various tumors harbor somatic mutations causing defective DDR/DNA repair. The concept of synthetic lethality can be exploited in such malignancies, as exemplified by approval of poly(ADP-ribose) polymerase inhibitors for treating BRCA1/2 mutated ovarian cancers. Herein, we detail how cellular DDR processes engage various proteins that sense DNA damage, initiate signaling pathways to promote cell cycle checkpoint activation, trigger apoptosis and coordinate DNA repair. We focus on novel therapeutic strategies targeting promising DDR targets and discuss challenges of patient selection and the development of rational drug combinations.