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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2020

01-12-2020 | Ovarian Cancer | Review

Participation of the ATR/CHK1 pathway in replicative stress targeted therapy of high-grade ovarian cancer

Authors: Patrycja Gralewska, Arkadiusz Gajek, Agnieszka Marczak, Aneta Rogalska

Published in: Journal of Hematology & Oncology | Issue 1/2020

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Abstract

Ovarian cancer is one of the most lethal gynecologic malignancies reported throughout the world. The initial, standard-of-care, adjuvant chemotherapy in epithelial ovarian cancer is usually a platinum drug, such as cisplatin or carboplatin, combined with a taxane. However, despite surgical removal of the tumor and initial high response rates to first-line chemotherapy, around 80% of women will develop cancer recurrence. Effective strategies, including chemotherapy and new research models, are necessary to improve the prognosis. The replication stress response (RSR) is characteristic of the development of tumors, including ovarian cancer. Hence, RSR pathway and DNA repair proteins have emerged as a new area for anticancer drug development. Although clinical trials have shown poly (ADP-ribose) polymerase inhibitors (PARPi) response rates of around 40% in women who carry a mutation in the BRCA1/2 genes, PARPi is responsible for tumor suppression, but not for complete tumor regression. Recent reports suggest that cells with impaired homologous recombination (HR) activities due to mutations in TP53 gene or specific DNA repair proteins are specifically sensitive to ataxia telangiectasia and Rad3-related protein (ATR) inhibitors. Replication stress activates DNA repair checkpoint proteins (ATR, CHK1), which prevent further DNA damage. This review describes the use of DNA repair checkpoint inhibitors as single agents and strategies combining these inhibitors with DNA-damaging compounds for ovarian cancer therapy, as well as the new platforms used for optimizing ovarian cancer therapy.
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Metadata
Title
Participation of the ATR/CHK1 pathway in replicative stress targeted therapy of high-grade ovarian cancer
Authors
Patrycja Gralewska
Arkadiusz Gajek
Agnieszka Marczak
Aneta Rogalska
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2020
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-020-00874-6

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