DNA damage repair in breast cancer and its therapeutic implications

Ali, Reem; Rakha, Emad A.; Madhusudan, Srinivasan; Bryant, Helen E.

Abstract

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.

Citation

Ali, R., Rakha, E. A., Madhusudan, S., & Bryant, H. E. (2017). DNA damage repair in breast cancer and its therapeutic implications. Pathology, 49(2), 156-165. doi:10.1016/j.pathol.2016.11.002

• Journal Article Type: Article
• Acceptance Date: Nov 2, 2016
• Online Publication Date: Dec 26, 2016
• Publication Date: Feb 28, 2017
• Deposit Date: Nov 21, 2018
• Journal: Pathology
• Print ISSN: 0031-3025
• Publisher: Lippincott, Williams & Wilkins
• Peer Reviewed: Peer Reviewed
• Volume: 49
• Issue: 2
• Pages: 156-165
• DOI: https://doi.org/10.1016/j.pathol.2016.11.002
• Keywords: Pathology and Forensic Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/1293801
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S0031302516404174?via%3Dihub