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: Elizabeth Alli, James M Ford
• Journal: DNA repair (DNA Repair (Amst)) Vol. 11 Issue 5 Pg. 522-4 (May 01 2012) ISSN: 1568-7856 [Electronic] Netherlands
• PMID: 22425348 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

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