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Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11

SIMPLE SUMMARY: Chemotherapeutic DNA-damaging agents targeting replication are widely used but predictive rationales for drug combinations and patient selection still need clinical definition. Here, we review cancer-associated replication stress (RepStress) and its genomic signature, and propose how...

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Autores principales: Jo, Ukhyun, Murai, Yasuhisa, Takebe, Naoko, Thomas, Anish, Pommier, Yves
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465591/
https://www.ncbi.nlm.nih.gov/pubmed/34572827
http://dx.doi.org/10.3390/cancers13184601
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author Jo, Ukhyun
Murai, Yasuhisa
Takebe, Naoko
Thomas, Anish
Pommier, Yves
author_facet Jo, Ukhyun
Murai, Yasuhisa
Takebe, Naoko
Thomas, Anish
Pommier, Yves
author_sort Jo, Ukhyun
collection PubMed
description SIMPLE SUMMARY: Chemotherapeutic DNA-damaging agents targeting replication are widely used but predictive rationales for drug combinations and patient selection still need clinical definition. Here, we review cancer-associated replication stress (RepStress) and its genomic signature, and propose how to utilize RepStress-targeted therapies in the context of ATR inhibitors and Schlafen 11 (SLFN11). ABSTRACT: Precision medicine aims to implement strategies based on the molecular features of tumors and optimized drug delivery to improve cancer diagnosis and treatment. DNA replication is a logical approach because it can be targeted by a broad range of anticancer drugs that are both clinically approved and in development. These drugs increase deleterious replication stress (RepStress); however, how to selectively target and identify the tumors with specific molecular characteristics are unmet clinical needs. Here, we provide background information on the molecular processes of DNA replication and its checkpoints, and discuss how to target replication, checkpoint, and repair pathways with ATR inhibitors and exploit Schlafen 11 (SLFN11) as a predictive biomarker.
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spelling pubmed-84655912021-09-27 Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11 Jo, Ukhyun Murai, Yasuhisa Takebe, Naoko Thomas, Anish Pommier, Yves Cancers (Basel) Review SIMPLE SUMMARY: Chemotherapeutic DNA-damaging agents targeting replication are widely used but predictive rationales for drug combinations and patient selection still need clinical definition. Here, we review cancer-associated replication stress (RepStress) and its genomic signature, and propose how to utilize RepStress-targeted therapies in the context of ATR inhibitors and Schlafen 11 (SLFN11). ABSTRACT: Precision medicine aims to implement strategies based on the molecular features of tumors and optimized drug delivery to improve cancer diagnosis and treatment. DNA replication is a logical approach because it can be targeted by a broad range of anticancer drugs that are both clinically approved and in development. These drugs increase deleterious replication stress (RepStress); however, how to selectively target and identify the tumors with specific molecular characteristics are unmet clinical needs. Here, we provide background information on the molecular processes of DNA replication and its checkpoints, and discuss how to target replication, checkpoint, and repair pathways with ATR inhibitors and exploit Schlafen 11 (SLFN11) as a predictive biomarker. MDPI 2021-09-14 /pmc/articles/PMC8465591/ /pubmed/34572827 http://dx.doi.org/10.3390/cancers13184601 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Jo, Ukhyun
Murai, Yasuhisa
Takebe, Naoko
Thomas, Anish
Pommier, Yves
Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11
title Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11
title_full Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11
title_fullStr Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11
title_full_unstemmed Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11
title_short Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11
title_sort precision oncology with drugs targeting the replication stress, atr, and schlafen 11
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465591/
https://www.ncbi.nlm.nih.gov/pubmed/34572827
http://dx.doi.org/10.3390/cancers13184601
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