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

Loboda, Anna P.; Adonin, Leonid S.; Zvereva, Svetlana D.; Guschin, Dmitri Y.; Korneenko, Tatyana V.; Telegina, Alexandra V.; Kondratieva, Olga K.; Frolova, Sofia E.; Pestov, Nikolay B.; Barlev, Nick A.

doi:10.3390/ijms24054982

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

by

Anna P. Loboda

¹,

Leonid S. Adonin

²

,

Svetlana D. Zvereva

¹,

Dmitri Y. Guschin

³

,

Tatyana V. Korneenko

⁴,

Alexandra V. Telegina

²,

Olga K. Kondratieva

²

,

Sofia E. Frolova

²,

Nikolay B. Pestov

^2,4,5,* and

Nick A. Barlev

^2,3,5,6,*

¹

Laboratory of Molecular Oncology, Phystech School of Biological and Medical Physics, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia

²

Institute of Biomedical Chemistry, 119121 Moscow, Russia

³

School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan

⁴

Group of Cross-Linking Enzymes, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia

⁵

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products, 108819 Moscow, Russia

⁶

Institute of Cytology, Tikhoretsky ave 4, 194064 St-Petersburg, Russia

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2023, 24(5), 4982; https://doi.org/10.3390/ijms24054982

Submission received: 11 February 2023 / Revised: 27 February 2023 / Accepted: 2 March 2023 / Published: 5 March 2023

(This article belongs to the Special Issue New Insights into the Pathophysiology of Gynecological Cancers 2.0)

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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 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.

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

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MDPI and ACS Style

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. https://doi.org/10.3390/ijms24054982

AMA Style

Loboda AP, Adonin LS, Zvereva SD, Guschin DY, Korneenko TV, Telegina AV, Kondratieva OK, Frolova SE, Pestov NB, Barlev NA. BRCA Mutations—The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers. International Journal of Molecular Sciences. 2023; 24(5):4982. https://doi.org/10.3390/ijms24054982

Chicago/Turabian Style

Loboda, Anna P., Leonid S. Adonin, Svetlana D. Zvereva, Dmitri Y. Guschin, Tatyana V. Korneenko, Alexandra V. Telegina, Olga K. Kondratieva, Sofia E. Frolova, Nikolay B. Pestov, and Nick A. Barlev. 2023. "BRCA Mutations—The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers" International Journal of Molecular Sciences 24, no. 5: 4982. https://doi.org/10.3390/ijms24054982

APA Style

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. (2023). BRCA Mutations—The Achilles Heel of Breast, Ovarian and Other Epithelial Cancers. International Journal of Molecular Sciences, 24(5), 4982. https://doi.org/10.3390/ijms24054982

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

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