The Fanconi Anemia/BRCA signaling pathway: disruption in cisplatin-sensitive ovarian cancers.
Ovarian tumors often exhibit chromosome instability and hypersensitivity to the chemotherapeutic agent cisplatin. Recently, we have shown that this cellular phenotype may result from an acquired disruption of the Fanconi Anemia/BRCA (FA/BRCA) signaling pathway. Disruption results from methylation and silencing of one of the FA genes (FANCF), leading to cisplatin sensitivity. Restoration of this pathway is associated with demethylation of FANCF, leading to acquired cisplatinum resistance. The serial inactivation and reactivation of the FA/BRCA pathway has important implications for the diagnosis and treatment of ovarian cancers and related cancers.
D'Andrea
Alan D
AD
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA. alan_dandrea@dfci.harvard.edu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D043171:Chromosomal Instability / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects; D004260:DNA Repair / Q000502:physiology; D005199:Fanconi Anemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D052219:Fanconi Anemia Complementation Group F Protein; D005260:Female; D051548:Histone Acetyltransferases; D056488:Histone Chaperones; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000092468:Bromodomain Containing Proteins
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D002945:Cisplatin; D052219:Fanconi Anemia Complementation Group F Protein; D051548:Histone Acetyltransferases; D056488:Histone Chaperones; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C499901:FANCF protein, human; C402649:BRD1 protein, human; D000092468:Bromodomain Containing Proteins