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Targeting DNA Replication Stress and DNA Double-Strand Break Repair for Optimizing SCLC Treatment
Small cell lung cancer (SCLC), accounting for about 15% of all cases of lung cancer worldwide, is the most lethal form of lung cancer. Despite an initially high response rate of SCLC to standard treatment, almost all patients are invariably relapsed within one year. Effective therapeutic strategies...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770306/ https://www.ncbi.nlm.nih.gov/pubmed/31480716 http://dx.doi.org/10.3390/cancers11091289 |
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author | Bian, Xing Lin, Wenchu |
author_facet | Bian, Xing Lin, Wenchu |
author_sort | Bian, Xing |
collection | PubMed |
description | Small cell lung cancer (SCLC), accounting for about 15% of all cases of lung cancer worldwide, is the most lethal form of lung cancer. Despite an initially high response rate of SCLC to standard treatment, almost all patients are invariably relapsed within one year. Effective therapeutic strategies are urgently needed to improve clinical outcomes. Replication stress is a hallmark of SCLC due to several intrinsic factors. As a consequence, constitutive activation of the replication stress response (RSR) pathway and DNA damage repair system is involved in counteracting this genotoxic stress. Therefore, therapeutic targeting of such RSR and DNA damage repair pathways will be likely to kill SCLC cells preferentially and may be exploited in improving chemotherapeutic efficiency through interfering with DNA replication to exert their functions. Here, we summarize potentially valuable targets involved in the RSR and DNA damage repair pathways, rationales for targeting them in SCLC treatment and ongoing clinical trials, as well as possible predictive biomarkers for patient selection in the management of SCLC. |
format | Online Article Text |
id | pubmed-6770306 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67703062019-10-30 Targeting DNA Replication Stress and DNA Double-Strand Break Repair for Optimizing SCLC Treatment Bian, Xing Lin, Wenchu Cancers (Basel) Review Small cell lung cancer (SCLC), accounting for about 15% of all cases of lung cancer worldwide, is the most lethal form of lung cancer. Despite an initially high response rate of SCLC to standard treatment, almost all patients are invariably relapsed within one year. Effective therapeutic strategies are urgently needed to improve clinical outcomes. Replication stress is a hallmark of SCLC due to several intrinsic factors. As a consequence, constitutive activation of the replication stress response (RSR) pathway and DNA damage repair system is involved in counteracting this genotoxic stress. Therefore, therapeutic targeting of such RSR and DNA damage repair pathways will be likely to kill SCLC cells preferentially and may be exploited in improving chemotherapeutic efficiency through interfering with DNA replication to exert their functions. Here, we summarize potentially valuable targets involved in the RSR and DNA damage repair pathways, rationales for targeting them in SCLC treatment and ongoing clinical trials, as well as possible predictive biomarkers for patient selection in the management of SCLC. MDPI 2019-09-02 /pmc/articles/PMC6770306/ /pubmed/31480716 http://dx.doi.org/10.3390/cancers11091289 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Bian, Xing Lin, Wenchu Targeting DNA Replication Stress and DNA Double-Strand Break Repair for Optimizing SCLC Treatment |
title | Targeting DNA Replication Stress and DNA Double-Strand Break Repair for Optimizing SCLC Treatment |
title_full | Targeting DNA Replication Stress and DNA Double-Strand Break Repair for Optimizing SCLC Treatment |
title_fullStr | Targeting DNA Replication Stress and DNA Double-Strand Break Repair for Optimizing SCLC Treatment |
title_full_unstemmed | Targeting DNA Replication Stress and DNA Double-Strand Break Repair for Optimizing SCLC Treatment |
title_short | Targeting DNA Replication Stress and DNA Double-Strand Break Repair for Optimizing SCLC Treatment |
title_sort | targeting dna replication stress and dna double-strand break repair for optimizing sclc treatment |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770306/ https://www.ncbi.nlm.nih.gov/pubmed/31480716 http://dx.doi.org/10.3390/cancers11091289 |
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