Breast cancers with compromised DNA repair exhibit selective sensitivity to elesclomol

DNA Repair (Amst). 2012 May 1;11(5):522-4. doi: 10.1016/j.dnarep.2012.02.003. Epub 2012 Mar 14.

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • DNA Damage / drug effects
  • DNA Repair / drug effects*
  • Female
  • Genes, BRCA1
  • Humans
  • Hydrazines / pharmacology*
  • Hydrazines / therapeutic use
  • Mice
  • Mutation
  • Reactive Oxygen Species / metabolism
  • Receptor, ErbB-2 / genetics

Substances

  • Antineoplastic Agents
  • Hydrazines
  • Reactive Oxygen Species
  • elesclomol
  • Receptor, ErbB-2