The Tumor Suppressor BRCA1/2, Cancer Susceptibility and Genome Instability in Gynecological and Mammary Cancers

Document Type : Systematic Review and Meta-analysis

Authors

1 Laboratory of Biology of Human Pathologies (BioPatH), Faculty of Sciences, Mohammed V University in Rabat, Rabat, Morocco.

2 Medical Biotechnology Center, Moroccan Foundation for Advanced Science, Innovation and Research (MAScIR), Rabat, Morocco.

Abstract

BRCA1 and BRCA2 germline alterations highly predispose women to breast and ovarian cancers they are mostly found within the TNBC (Triple-Negative Breast Cancer) and the HGSOC (High-Grade Serous Ovarian Carcinoma) subsets, known by an aggressive phenotype, the lack of therapeutic targets and poor prognosis. Importantly, there is an increased risk for cervical cancer in BRCA1 and BRCA2 mutation carriers that raises questions about the link between the HPV-driven genome instability and BRCA1 and BRCA2 germline mutations. Clinical, preclinical, and in vitro studies for precision and clarityexplained the increased risk for breast and ovarian cancers by genome instability resulting from the lack or loss of many functions related to BRCA1 or BRCA2 proteins such as DNA damage repair, stalled forks and R-loops resolution, transcription regulation, cell cycle control, and oxidative stress. In this review, we decipher the relationship between BRCA1/2 alterations and genomic instability leading to gynecomammary cancers through results from patients, mice, and cell lines. Understanding the early events of BRCA1/2-driven genomic instability in gynecomammary cancers would help to find new biomarkers for early diagnosis, improve the sensitivity of emerging therapies such as PARP inhibitors, and reveal new potential therapeutic targets.

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Volume 24, Issue 9
September 2023
Pages 3139-3153
  • Receive Date: 04 April 2023
  • Revise Date: 03 July 2023
  • Accept Date: 10 September 2023
  • First Publish Date: 10 September 2023