Exploiting the Fanconi Anemia Pathway for Targeted Anti-Cancer Therapy

Abstract

Genome instability, primarily caused by faulty DNA repair mechanisms, drives tumorigenesis. Therapeutic interven-tions that exploit deregulated DNA repair in cancer have made considerable progress by targeting tumor-specific alterations of DNA repair factors, which either induces synthetic lethality or augments the efficacy of convention-al chemotherapy and radiotherapy. The study of Fanconi anemia (FA), a rare inherited blood disorder and cancer predisposition syndrome, has been instrumental in under-standing the extent to which DNA repair defects contribute to tumorigenesis. The FA pathway functions to resolve blocked replication forks in response to DNA interstrand cross-links (ICLs), and accumulating knowledge of its ac-tivation by the ubiquitin-mediated signaling pathway has provided promising therapeutic opportunities for cancer treatment. Here, we discuss recent advances in our under-standing of FA pathway regulation and its potential appli-cation for designing tailored therapeutics that take ad-vantage of deregulated DNA ICL repair in cancer