Breast Cancer Predisposition Genes and Synthetic Lethality

International Journal of Molecular Sciences

HannahE. Neiger¹  Yihui Shi²  EmilyL. Siegler² 

[1] College of Graduate Studies, California Northstate University, Elk Grove, CA 95757, USA;College of Medicine, California Northstate University, Elk Grove, CA 95757, USA;

关键词: BRCA1/BRCA2;    CPGs;    PARPi;    hereditary breast cancer;    synthetic lethality;    DNA repair;   

DOI  :  10.3390/ijms22115614

来源: DOAJ

【 摘 要 】

BRCA1 and BRCA2 are tumor suppressor genes with pivotal roles in the development of breast and ovarian cancers. These genes are essential for DNA double-strand break repair via homologous recombination (HR), which is a virtually error-free DNA repair mechanism. Following BRCA1 or BRCA2 mutations, HR is compromised, forcing cells to adopt alternative error-prone repair pathways that often result in tumorigenesis. Synthetic lethality refers to cell death caused by simultaneous perturbations of two genes while change of any one of them alone is nonlethal. Therefore, synthetic lethality can be instrumental in identifying new therapeutic targets for BRCA1/2 mutations. PARP is an established synthetic lethal partner of the BRCA genes. Its role is imperative in the single-strand break DNA repair system. Recently, Olaparib (a PARP inhibitor) was approved for treatment of BRCA1/2 breast and ovarian cancer as the first successful synthetic lethality-based therapy, showing considerable success in the development of effective targeted cancer therapeutics. Nevertheless, the possibility of drug resistance to targeted cancer therapy based on synthetic lethality necessitates the development of additional therapeutic options. This literature review addresses cancer predisposition genes, including BRCA1, BRCA2, and PALB2, synthetic lethality in the context of DNA repair machinery, as well as available treatment options.

【 授权许可】

Unknown