BRCA Mutations—The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers
Loboda A.P. Adonin L.S. Zvereva S.D. Guschin D.Y. Korneenko T.V. Telegina A.V. Kondratieva O.K. Frolova S.E. Pestov N.B. Barlev N.A.
March 2023Multidisciplinary Digital Publishing Institute (MDPI)
International Journal of Molecular Sciences
2023#24Issue 5
Two related tumor suppressor genes, BRCA1 and BRCA2, attract a lot of attention from both fundamental and clinical points of view. Oncogenic hereditary mutations in these genes are firmly linked to the early onset of breast and ovarian cancers. However, the molecular mechanisms that drive extensive mutagenesis in these genes are not known. In this review, we hypothesize that one of the potential mechanisms behind this phenomenon can be mediated by Alu mobile genomic elements. Linking mutations in the BRCA1 and BRCA2 genes to the general mechanisms of genome stability and DNA repair is critical to ensure the rationalized choice of anti-cancer therapy. Accordingly, we review the literature available on the mechanisms of DNA damage repair where these proteins are involved, and how the inactivating mutations in these genes (BRCAness) can be exploited in anti-cancer therapy. We also discuss a hypothesis explaining why breast and ovarian epithelial tissues are preferentially susceptible to mutations in BRCA genes. Finally, we discuss prospective novel therapeutic approaches for treating BRCAness cancers.
Alu repeats , breast cancer , ovarian cancer , PARP inhibitors , protein-protein interactions
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Laboratory of Molecular Oncology, Phystech School of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russian Federation
Institute of Biomedical Chemistry, Moscow, 119121, Russian Federation
School of Medicine, Nazarbayev University, Astana, 010000, Kazakhstan
Group of Cross-Linking Enzymes, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russian Federation
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products, Moscow, 108819, Russian Federation
Institute of Cytology, Tikhoretsky ave 4, St-Petersburg, 194064, Russian Federation
Laboratory of Molecular Oncology
Institute of Biomedical Chemistry
School of Medicine
Group of Cross-Linking Enzymes
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products
Institute of Cytology
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