title: Breast cancers with compromised DNA repair exhibit selective sensitivity to elesclomol.
abstract: The basal-like subtype of breast cancers, including those that contain germline mutations in BRCA1, tend to be triple-negative (i.e. lack expression of estrogen and progesterone receptors and lack overexpression/amplification of the HER2/neu oncogene), which renders them relatively insensitive to existing "targeted" therapy. BRCA1-mutated and basal-like breast cancers harbor compromised ability for repairing oxidative DNA damage by the DNA base-excision repair pathway. We found that this defective repair mechanism predicts sensitivity to elesclomol, an experimental therapeutic that produces elevated levels of oxidative DNA damage. In conclusion, BRCA1-mutated and/or basal-like breast cancers may benefit from treatment regimens that include elesclomol.
authors.affiliation: Stanford University-School of Medicine, Department of Medicine Oncology, 269 Campus Drive, Stanford, CA 93405, USA. ealli@stanford.edu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Alli
authors.forename: James M
authors.initials: JM
authors.lastname: Ford
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D006834:Hydrazines; D017382:Reactive Oxygen Species; D018719:Erb-b2 Receptor Tyrosine Kinases; C512195:elesclomol