Stanford University-School of Medicine, Department of Medicine Oncology, 269 Campus Drive, Stanford, CA 93405, USA.
DNA Repair (Amst). 2012 May 1;11(5):522-4. doi: 10.1016/j.dnarep.2012.02.003. Epub 2012 Mar 14.
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.
基底样乳腺癌亚型，包括那些携带 BRCA1 种系突变的乳腺癌，往往是三阴性（即缺乏雌激素和孕激素受体的表达，并且缺乏 HER2/neu 癌基因的过表达/扩增），这使得它们对现有的“靶向”治疗相对不敏感。BRCA1 突变和基底样乳腺癌通过 DNA 碱基切除修复途径修复氧化 DNA 损伤的能力受损。我们发现，这种有缺陷的修复机制预示着对 elesclomol 的敏感性，elesclomol 是一种产生高水平氧化 DNA 损伤的实验性治疗药物。总之，BRCA1 突变和/或基底样乳腺癌可能受益于包括 elesclomol 在内的治疗方案。
