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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8465591 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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