Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

BRCA Mutations: The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers

Anna P. Loboda
,
Leonid S. Adonin
ORCID logo ,
Svetlana D. Zvereva
,
Nikolay B. Pestov
* ,
Dmitri Y. Guschin
,
Tatyana V. Korneenko
,
Alexandra V. Telegina
,
Olga K. Kondratieva
,
Sofia E. Frolova
,
Nickolai A. Barlev
*
Version 1 : Received: 11 February 2023 / Approved: 13 February 2023 / Online: 13 February 2023 (07:54:35 CET)

A peer-reviewed article of this Preprint also exists.

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. BRCA Mutations—The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers. Int. J. Mol. Sci. 2023, 24, 4982. 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. BRCA Mutations—The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers. Int. J. Mol. Sci. 2023, 24, 4982.

Abstract

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 mechanism(s) of genome stability and DNA repair is critical to ensure the rationalized choice of anti-cancer therapy. Accordingly, we review the literature available on mechanisms of DNA damage repair where these proteins are involved in and how the inactivating mutations in these genes (BRCAness) can be exploited in anti-cancer therapy. We also propose a hypothesis that explains why breast and ovarian epithelial tissues are preferentially susceptible to mutations in BRCA genes. Finally, we discuss perspectives of novel therapeutic approaches for treating BRCAness cancers.

Keywords

breast cancer; ovarian cancer; PARP inhibitors; Alu repeats; protein-protein interactions

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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