DNA damage repair in breast cancer and its therapeutic implications

详细信息    查看全文

• 作者：Reem Ali¹ ; ² ; Emad A. Rakha¹ ; ² ; Srinivasan Madhusudan¹ ; ² ; Helen E. Bryant³ ; ^{h.bryant@sheffield.ac.uk}
• 关键词：DNA damage response ; breast cancer ; DDR ; defects ; therapeutic implications
• 刊名：Pathology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：49
• 期：2
• 页码：156-165
• 全文大小：298 K
• 卷排序：49

文摘

The DNA damage response (DDR) involves the activation of numerous cellular activities that repair DNA lesions and maintain genomic integrity, and is critical in preventing tumorigenesis. Inherited or acquired mutations in specific genes involved in the DNA damage response, for example the breast cancer susceptibility genes 1/2 (BRCA1/2), phosphatase and tensin homolog (PTEN) and P53 are associated with various subtypes of breast cancer. Such changes can render breast cancer cells particularly sensitive to specific DNA damage response inhibitors, for example BRCA1/2 germline mutated cells are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. The aims of this review are to discuss specific DNA damage response defects in breast cancer and to present the current stage of development of various DDR inhibitors (namely PARP, ATM/ATR, DNA-PK, PARG, RECQL5, FEN1 and APE1) for breast cancer mono- and combination therapy.