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Checkpoint inhibitors in ovarian cancer: A review of preclinical data

Ovarian cancer is the deadliest gynecologic malignancy, and relapse after initial treatment is frequently fatal. Although ovarian cancer typically has an immunosuppressive tumor microenvironment, a strong intratumoral T cell presence is associated with an improved response to chemotherapy and better...

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Autores principales: Doo, David W., Norian, Lyse A., Arend, Rebecca C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609798/
https://www.ncbi.nlm.nih.gov/pubmed/31312712
http://dx.doi.org/10.1016/j.gore.2019.06.003
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author Doo, David W.
Norian, Lyse A.
Arend, Rebecca C.
author_facet Doo, David W.
Norian, Lyse A.
Arend, Rebecca C.
author_sort Doo, David W.
collection PubMed
description Ovarian cancer is the deadliest gynecologic malignancy, and relapse after initial treatment is frequently fatal. Although ovarian cancer typically has an immunosuppressive tumor microenvironment, a strong intratumoral T cell presence is associated with an improved response to chemotherapy and better overall prognosis. Given the success of checkpoint inhibitors in the treatment of other malignancies, there has been an attempt to replicate these results in ovarian cancer clinical trials. Preclincal studies in ovarian cancer have also been conducted over the past decade, and most of the focus has been on the use of programmed cell death protein 1 (PD-1). Several other checkpoint inhibitors have also been investigated in various combinations with chemotherapy, oncolytic vaccines, co-stimulatory molecules, poly ADP ribose polymerase (PARP) inhibitors, and other checkpoint inhibitors. Unfortunately, these successes have yet to translate to the clinical realm. Whether this is because the drug class is truly ineffective in ovarian cancer, or simply because the research is lacking is unclear. Either way, it is evident that preclinical data on the use of checkpoint inhibitors is woefully deficient in ovarian cancer and more research is urgently needed to inform the translation of immune checkpoint blockade into successful clinical use. In this review, we discuss the results from preclinical studies using checkpoint inhibitors to treat ovarian cancer, with a focus on strategies that show potential for clinical use.
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spelling pubmed-66097982019-07-16 Checkpoint inhibitors in ovarian cancer: A review of preclinical data Doo, David W. Norian, Lyse A. Arend, Rebecca C. Gynecol Oncol Rep Narrative Review Ovarian cancer is the deadliest gynecologic malignancy, and relapse after initial treatment is frequently fatal. Although ovarian cancer typically has an immunosuppressive tumor microenvironment, a strong intratumoral T cell presence is associated with an improved response to chemotherapy and better overall prognosis. Given the success of checkpoint inhibitors in the treatment of other malignancies, there has been an attempt to replicate these results in ovarian cancer clinical trials. Preclincal studies in ovarian cancer have also been conducted over the past decade, and most of the focus has been on the use of programmed cell death protein 1 (PD-1). Several other checkpoint inhibitors have also been investigated in various combinations with chemotherapy, oncolytic vaccines, co-stimulatory molecules, poly ADP ribose polymerase (PARP) inhibitors, and other checkpoint inhibitors. Unfortunately, these successes have yet to translate to the clinical realm. Whether this is because the drug class is truly ineffective in ovarian cancer, or simply because the research is lacking is unclear. Either way, it is evident that preclinical data on the use of checkpoint inhibitors is woefully deficient in ovarian cancer and more research is urgently needed to inform the translation of immune checkpoint blockade into successful clinical use. In this review, we discuss the results from preclinical studies using checkpoint inhibitors to treat ovarian cancer, with a focus on strategies that show potential for clinical use. Elsevier 2019-06-18 /pmc/articles/PMC6609798/ /pubmed/31312712 http://dx.doi.org/10.1016/j.gore.2019.06.003 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Narrative Review
Doo, David W.
Norian, Lyse A.
Arend, Rebecca C.
Checkpoint inhibitors in ovarian cancer: A review of preclinical data
title Checkpoint inhibitors in ovarian cancer: A review of preclinical data
title_full Checkpoint inhibitors in ovarian cancer: A review of preclinical data
title_fullStr Checkpoint inhibitors in ovarian cancer: A review of preclinical data
title_full_unstemmed Checkpoint inhibitors in ovarian cancer: A review of preclinical data
title_short Checkpoint inhibitors in ovarian cancer: A review of preclinical data
title_sort checkpoint inhibitors in ovarian cancer: a review of preclinical data
topic Narrative Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609798/
https://www.ncbi.nlm.nih.gov/pubmed/31312712
http://dx.doi.org/10.1016/j.gore.2019.06.003
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