TY - JOUR
T1 - The Tumor Suppressor BRCA1/2, Cancer Susceptibility and Genome Instability in Gynecological and Mammary Cancers
AU - Oubaddou, Yassire
AU - Ali, Fatima Ben
AU - Oubaqui, Fatima Ezzahrae
AU - Qmichou, Zineb
AU - Bakri, Youssef
AU - El Hassani, Rabii Ameziane
N1 - Publisher Copyright:
© This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - 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.
AB - 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.
KW - BRCA1-BRCA2
KW - breast cancer
KW - cervical cancer
KW - genome instability
KW - gynecomammary cancers
KW - ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=85172825032&partnerID=8YFLogxK
U2 - 10.31557/APJCP.2023.24.9.3139
DO - 10.31557/APJCP.2023.24.9.3139
M3 - Review article
C2 - 37774066
AN - SCOPUS:85172825032
SN - 1513-7368
VL - 24
SP - 3139
EP - 3153
JO - Asian Pacific Journal of Cancer Prevention
JF - Asian Pacific Journal of Cancer Prevention
IS - 9
ER -