Abstract IA06: The Fanconi anemia-BRCA pathway and cancer

Abstract

Abstract The Fanconi anemia (FA)-BRCA pathway has emerged as an important pathway in cancer biology. FA is a rare genetic disease characterized by chromosomal instability, cancer-susceptibility and cellular sensitivity to interstrand DNA crosslink (ICL)-inducing agents. The FA proteins including breast/ovarian cancer susceptibility proteins, BRCA1(FANCS) and BRCA2(FANCD1), cooperate in a common pathway (the FA-BRCA pathway) required for cellular resistance to ICL-inducing agents. The main function of the pathway is to coordinate multiple DNA repair mechanisms during ICL repair, although many of the components of the pathway also play critical roles in protecting replication forks. Inactivation of this pathway in cancer cells can lead to sensitivity to anti-cancer ICL-inducing agents, such as cisplatin and carboplatin, while reactivation of this pathway is implicated in acquired resistance to ICL-inducing agents. Therefore, inhibition of the pathway is an attractive therapeutic strategy to overcome DNA-crosslinker resistance of tumor cells. In this talk, I will introduce what the FA-BRCA pathway is and how this pathway is inactivated in human cancer. I will also mention some of the mechanisms of acquired resistance to cisplatin and PARP inhibitors in cancer cells, related to the FA-BRCA pathway. I will also discuss our recent findings about the regulation of the FA-BRCA pathway by FANCI protein and a deubiquitinating enzyme, USP28. Citation Format: Toshiyasu Taniguchi. The Fanconi anemia-BRCA pathway and cancer [abstract]. In: Proceedings of the AACR Special Conference on DNA Repair: Tumor Development and Therapeutic Response; 2016 Nov 2-5; Montreal, QC, Canada. Philadelphia (PA): AACR; Mol Cancer Res 2017;15(4_Suppl):Abstract nr IA06.