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Exploring Better Strategies for RAS Mutation-Associated EGFR-Targeted Resistance in Colorectal Cancer: From the Perspective of Cancer Community Ecology

RAS is the most common mutated gene in colorectal cancer (CRC), and its occurrence is associated with primary and acquired resistance to anti-epidermal growth factor receptor (EGFR) blockade. Cancer community ecology, such as the competitive exclusion principle, is a valuable focus and would contrib...

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Autores principales: Wang, Xiaojie, Wu, Wenchuan, Zheng, Zhifang, Chi, Pan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568953/
https://www.ncbi.nlm.nih.gov/pubmed/34745987
http://dx.doi.org/10.3389/fonc.2021.754220
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author Wang, Xiaojie
Wu, Wenchuan
Zheng, Zhifang
Chi, Pan
author_facet Wang, Xiaojie
Wu, Wenchuan
Zheng, Zhifang
Chi, Pan
author_sort Wang, Xiaojie
collection PubMed
description RAS is the most common mutated gene in colorectal cancer (CRC), and its occurrence is associated with primary and acquired resistance to anti-epidermal growth factor receptor (EGFR) blockade. Cancer community ecology, such as the competitive exclusion principle, is a valuable focus and would contribute to the understanding of drug resistance. We have presented several articles on RAS mutant clonal evolution monitoring during anti-EGFR treatment in CRC. In these articles, the availability of serially collected samples provided a unique opportunity to model the tumor evolutionary process from the perspective of cancer community ecology in those patients upon treatment. In this perspective article, we presented a theoretical basis and evidence from several experimental or phase II clinical trials for the contemporary application of ecological mechanisms in CRC treatment. In general, a reduction in targetable RAS wild-type cells to a maximum tolerated extent, such as continuous treatment, might lead to the competitive release of inextirpable RAS mutant cells and cancer progression. A full understanding of subclonal competition might be beneficial in managing CRC. Several ecological strategies, including anti-EGFR treatment reintroduced at an appropriate point of time for RAS mutant patients, intermittent treatment instead of continuous treatment, the appropriate sequence of nonselective targeted therapy, and combination therapy, were proposed.
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spelling pubmed-85689532021-11-06 Exploring Better Strategies for RAS Mutation-Associated EGFR-Targeted Resistance in Colorectal Cancer: From the Perspective of Cancer Community Ecology Wang, Xiaojie Wu, Wenchuan Zheng, Zhifang Chi, Pan Front Oncol Oncology RAS is the most common mutated gene in colorectal cancer (CRC), and its occurrence is associated with primary and acquired resistance to anti-epidermal growth factor receptor (EGFR) blockade. Cancer community ecology, such as the competitive exclusion principle, is a valuable focus and would contribute to the understanding of drug resistance. We have presented several articles on RAS mutant clonal evolution monitoring during anti-EGFR treatment in CRC. In these articles, the availability of serially collected samples provided a unique opportunity to model the tumor evolutionary process from the perspective of cancer community ecology in those patients upon treatment. In this perspective article, we presented a theoretical basis and evidence from several experimental or phase II clinical trials for the contemporary application of ecological mechanisms in CRC treatment. In general, a reduction in targetable RAS wild-type cells to a maximum tolerated extent, such as continuous treatment, might lead to the competitive release of inextirpable RAS mutant cells and cancer progression. A full understanding of subclonal competition might be beneficial in managing CRC. Several ecological strategies, including anti-EGFR treatment reintroduced at an appropriate point of time for RAS mutant patients, intermittent treatment instead of continuous treatment, the appropriate sequence of nonselective targeted therapy, and combination therapy, were proposed. Frontiers Media S.A. 2021-10-22 /pmc/articles/PMC8568953/ /pubmed/34745987 http://dx.doi.org/10.3389/fonc.2021.754220 Text en Copyright © 2021 Wang, Wu, Zheng and Chi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wang, Xiaojie
Wu, Wenchuan
Zheng, Zhifang
Chi, Pan
Exploring Better Strategies for RAS Mutation-Associated EGFR-Targeted Resistance in Colorectal Cancer: From the Perspective of Cancer Community Ecology
title Exploring Better Strategies for RAS Mutation-Associated EGFR-Targeted Resistance in Colorectal Cancer: From the Perspective of Cancer Community Ecology
title_full Exploring Better Strategies for RAS Mutation-Associated EGFR-Targeted Resistance in Colorectal Cancer: From the Perspective of Cancer Community Ecology
title_fullStr Exploring Better Strategies for RAS Mutation-Associated EGFR-Targeted Resistance in Colorectal Cancer: From the Perspective of Cancer Community Ecology
title_full_unstemmed Exploring Better Strategies for RAS Mutation-Associated EGFR-Targeted Resistance in Colorectal Cancer: From the Perspective of Cancer Community Ecology
title_short Exploring Better Strategies for RAS Mutation-Associated EGFR-Targeted Resistance in Colorectal Cancer: From the Perspective of Cancer Community Ecology
title_sort exploring better strategies for ras mutation-associated egfr-targeted resistance in colorectal cancer: from the perspective of cancer community ecology
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568953/
https://www.ncbi.nlm.nih.gov/pubmed/34745987
http://dx.doi.org/10.3389/fonc.2021.754220
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