title: Exploiting the Fanconi Anemia Pathway for Targeted Anti-Cancer Therapy.
abstract: Genome instability, primarily caused by faulty DNA repair mechanisms, drives tumorigenesis. Therapeutic interventions 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 conventional chemotherapy and radiotherapy. The study of Fanconi anemia (FA), a rare inherited blood disorder and cancer predisposition syndrome, has been instrumental in understanding 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 activation by the ubiquitin-mediated signaling pathway has provided promising therapeutic opportunities for cancer treatment. Here, we discuss recent advances in our understanding of FA pathway regulation and its potential application for designing tailored therapeutics that take advantage of deregulated DNA ICL repair in cancer.
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, New York 11794, USA.
authors.forename: Ukhyun
authors.initials: U
authors.lastname: Jo
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, New York 11794, USA.
authors.forename: Hyungjin
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004249:DNA Damage; D004260:DNA Repair; D005199:Fanconi Anemia / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents
keywords: DNA interstrand cross-link; DNA repair; Fanconi anemia; cancer therapeutics; ubiquitin signaling