Imyanitov E, Sokolenko A. Mechanisms of acquired resistance of BRCA1/2-driven tumors to platinum compounds and PARP inhibitors. World J Clin Oncol 2021; 12(7): 544-556 [PMID: 34367927 DOI: 10.5306/wjco.v12.i7.544]
Corresponding Author of This Article
Evgeny Imyanitov, MD, Professor, Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Pesochny, Leningradskaya str. 68, Saint-Petersburg 197758, Russia. evgeny@imyanitov.spb.ru
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Clin Oncol. Jul 24, 2021; 12(7): 544-556 Published online Jul 24, 2021. doi: 10.5306/wjco.v12.i7.544
Mechanisms of acquired resistance of BRCA1/2-driven tumors to platinum compounds and PARP inhibitors
Evgeny Imyanitov, Anna Sokolenko
Evgeny Imyanitov, Anna Sokolenko, Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Saint-Petersburg 197758, Russia
Evgeny Imyanitov, Anna Sokolenko, Department of Medical Genetics, St.-Petersburg Pediatric Medical University, Saint-Petersburg 194100, Russia
Evgeny Imyanitov, Department of Oncology, I.I. Mechnikov North-Western Medical University, Saint-Petersburg 191015, Russia
Author contributions: Imyanitov E designed the concept of the paper and prepared the draft; Sokolenko A collected the data for the paper, designed the figures and contributed to the manuscript writing.
Supported byThe Ministry of Science and Higher Education of the Russian Federation, No. 075-15-2020-789.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Evgeny Imyanitov, MD, Professor, Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Pesochny, Leningradskaya str. 68, Saint-Petersburg 197758, Russia. evgeny@imyanitov.spb.ru
Received: February 3, 2021 Peer-review started: February 3, 2021 First decision: March 31, 2021 Revised: April 4, 2021 Accepted: June 3, 2021 Article in press: June 3, 2021 Published online: July 24, 2021
Core Tip
Core Tip: BRCA1/2-associated tumors are highly sensitive to platinum compounds and poly (ADP-ribose) polymerase inhibitors; however, they eventually acquire resistance to this type of therapy. Restoration of BRCA1/2 function via the second mutation is the most known mechanism of tumor adaptation to the therapeutic pressure. Some studies demonstrate that even chemonaive BRCA1-driven tumors contain a small fraction of BRCA1-proficient cells suggesting that the loss of the remaining allele of this gene is not the first event in tumor pathogenesis. These pre-existing platinum-resistant cells rapidly repopulate tumor mass during neoadjuvant therapy for ovarian cancer and explain inevitability of the disease relapses after seemingly successful surgical debulking.
