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Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors

Testicular germ cell tumors (TGCTs) are a cancer pharmacology success story with a majority of patients cured even in the highly advanced and metastatic setting. Successful treatment of TGCTs is primarily due to the exquisite responsiveness of this solid tumor to cisplatin-based therapy. However, a...

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Autores principales: Singh, Ratnakar, Fazal, Zeeshan, Freemantle, Sarah J., Spinella, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: OAE Publishing Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752046/
https://www.ncbi.nlm.nih.gov/pubmed/31538140
http://dx.doi.org/10.20517/cdr.2019.19
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author Singh, Ratnakar
Fazal, Zeeshan
Freemantle, Sarah J.
Spinella, Michael J.
author_facet Singh, Ratnakar
Fazal, Zeeshan
Freemantle, Sarah J.
Spinella, Michael J.
author_sort Singh, Ratnakar
collection PubMed
description Testicular germ cell tumors (TGCTs) are a cancer pharmacology success story with a majority of patients cured even in the highly advanced and metastatic setting. Successful treatment of TGCTs is primarily due to the exquisite responsiveness of this solid tumor to cisplatin-based therapy. However, a significant percentage of patients are, or become, refractory to cisplatin and die from progressive disease. Mechanisms for both clinical hypersensitivity and resistance have largely remained a mystery despite the promise of applying lessons to the majority of solid tumors that are not curable in the metastatic setting. Recently, this promise has been heightened by the realization that distinct (and perhaps pharmacologically replicable) epigenetic states, rather than fixed genetic alterations, may play dominant roles in not only TGCT etiology and progression but also their curability with conventional chemotherapies. In this review, it discusses potential mechanisms of TGCT cisplatin sensitivity and resistance to conventional chemotherapeutics.
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spelling pubmed-67520462019-09-19 Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors Singh, Ratnakar Fazal, Zeeshan Freemantle, Sarah J. Spinella, Michael J. Cancer Drug Resist Review Testicular germ cell tumors (TGCTs) are a cancer pharmacology success story with a majority of patients cured even in the highly advanced and metastatic setting. Successful treatment of TGCTs is primarily due to the exquisite responsiveness of this solid tumor to cisplatin-based therapy. However, a significant percentage of patients are, or become, refractory to cisplatin and die from progressive disease. Mechanisms for both clinical hypersensitivity and resistance have largely remained a mystery despite the promise of applying lessons to the majority of solid tumors that are not curable in the metastatic setting. Recently, this promise has been heightened by the realization that distinct (and perhaps pharmacologically replicable) epigenetic states, rather than fixed genetic alterations, may play dominant roles in not only TGCT etiology and progression but also their curability with conventional chemotherapies. In this review, it discusses potential mechanisms of TGCT cisplatin sensitivity and resistance to conventional chemotherapeutics. OAE Publishing Inc. 2019-09-19 /pmc/articles/PMC6752046/ /pubmed/31538140 http://dx.doi.org/10.20517/cdr.2019.19 Text en © The Author(s) 2019. https://creativecommons.org/licenses/by/4.0/© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Review
Singh, Ratnakar
Fazal, Zeeshan
Freemantle, Sarah J.
Spinella, Michael J.
Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors
title Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors
title_full Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors
title_fullStr Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors
title_full_unstemmed Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors
title_short Mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors
title_sort mechanisms of cisplatin sensitivity and resistance in testicular germ cell tumors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752046/
https://www.ncbi.nlm.nih.gov/pubmed/31538140
http://dx.doi.org/10.20517/cdr.2019.19
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