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The Evolving Biomarker Landscape for Treatment Selection in Metastatic Colorectal Cancer

The approval of targeted therapies for metastatic colorectal cancer (mCRC) has led to important improvements in patient outcomes. However, it is still necessary to increase individualisation of treatments based on tumour genetic profiles to optimise efficacy, while minimising toxicity. As such, ther...

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Autores principales: Taieb, Julien, Jung, Andreas, Sartore-Bianchi, Andrea, Peeters, Marc, Seligmann, Jenny, Zaanan, Aziz, Burdon, Peter, Montagut, Clara, Laurent-Puig, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728290/
https://www.ncbi.nlm.nih.gov/pubmed/31347092
http://dx.doi.org/10.1007/s40265-019-01165-2
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author Taieb, Julien
Jung, Andreas
Sartore-Bianchi, Andrea
Peeters, Marc
Seligmann, Jenny
Zaanan, Aziz
Burdon, Peter
Montagut, Clara
Laurent-Puig, Pierre
author_facet Taieb, Julien
Jung, Andreas
Sartore-Bianchi, Andrea
Peeters, Marc
Seligmann, Jenny
Zaanan, Aziz
Burdon, Peter
Montagut, Clara
Laurent-Puig, Pierre
author_sort Taieb, Julien
collection PubMed
description The approval of targeted therapies for metastatic colorectal cancer (mCRC) has led to important improvements in patient outcomes. However, it is still necessary to increase individualisation of treatments based on tumour genetic profiles to optimise efficacy, while minimising toxicity. As such, there is currently great focus on the discovery and validation of further biomarkers in mCRC, with many new potential prognostic and predictive markers being identified alongside developments in patient molecular profiling technologies. Here, we review data for validated and emerging biomarkers impacting treatment strategies in mCRC. We completed a structured literature search of the PubMed database to identify relevant publications, limiting for English-language publications published between 1 January 2014 and 11 July 2018. In addition, we performed a manual search of the key general oncology and CRC-focused congresses to identify abstracts reporting emerging mCRC biomarker data, and of ClinicalTrials.gov to identify ongoing clinical trials investigating emerging biomarkers in mCRC and/or molecular-guided clinical trials. There is solid evidence supporting the use of BRAF status as a prognostic biomarker and DYPD, UGT1A1, RAS, and microsatellite instability as predictive biomarkers in mCRC. There are a number of emerging biomarkers that may prove to be clinically relevant in the future to have prognostic (HPP1 methylation), predictive (HER3, microRNAs, anti-angiogenic markers, and CRC intrinsic subtypes), or both prognostic and predictive values (HER2, CpG island methylator phenotype, tumour mutational load, gene fusions, and consensus molecular subtypes). As such, new biomarker-led treatment strategies in addition to anti-epidermal growth factor receptor and anti-angiogenetic treatments are being explored. Biomarkers that are not recommended to be tested in clinical practice or are unlikely to be imminently clinically relevant for mCRC include thymidylate transferase, ERCC1, PIK3CA, and PTEN. We highlight the clinical utility of existing and emerging biomarkers in mCRC and provide recommended treatment strategies according to the biomarker status. An update on ongoing molecular-guided clinical trials is also provided.
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spelling pubmed-67282902019-09-20 The Evolving Biomarker Landscape for Treatment Selection in Metastatic Colorectal Cancer Taieb, Julien Jung, Andreas Sartore-Bianchi, Andrea Peeters, Marc Seligmann, Jenny Zaanan, Aziz Burdon, Peter Montagut, Clara Laurent-Puig, Pierre Drugs Review Article The approval of targeted therapies for metastatic colorectal cancer (mCRC) has led to important improvements in patient outcomes. However, it is still necessary to increase individualisation of treatments based on tumour genetic profiles to optimise efficacy, while minimising toxicity. As such, there is currently great focus on the discovery and validation of further biomarkers in mCRC, with many new potential prognostic and predictive markers being identified alongside developments in patient molecular profiling technologies. Here, we review data for validated and emerging biomarkers impacting treatment strategies in mCRC. We completed a structured literature search of the PubMed database to identify relevant publications, limiting for English-language publications published between 1 January 2014 and 11 July 2018. In addition, we performed a manual search of the key general oncology and CRC-focused congresses to identify abstracts reporting emerging mCRC biomarker data, and of ClinicalTrials.gov to identify ongoing clinical trials investigating emerging biomarkers in mCRC and/or molecular-guided clinical trials. There is solid evidence supporting the use of BRAF status as a prognostic biomarker and DYPD, UGT1A1, RAS, and microsatellite instability as predictive biomarkers in mCRC. There are a number of emerging biomarkers that may prove to be clinically relevant in the future to have prognostic (HPP1 methylation), predictive (HER3, microRNAs, anti-angiogenic markers, and CRC intrinsic subtypes), or both prognostic and predictive values (HER2, CpG island methylator phenotype, tumour mutational load, gene fusions, and consensus molecular subtypes). As such, new biomarker-led treatment strategies in addition to anti-epidermal growth factor receptor and anti-angiogenetic treatments are being explored. Biomarkers that are not recommended to be tested in clinical practice or are unlikely to be imminently clinically relevant for mCRC include thymidylate transferase, ERCC1, PIK3CA, and PTEN. We highlight the clinical utility of existing and emerging biomarkers in mCRC and provide recommended treatment strategies according to the biomarker status. An update on ongoing molecular-guided clinical trials is also provided. Springer International Publishing 2019-07-25 2019 /pmc/articles/PMC6728290/ /pubmed/31347092 http://dx.doi.org/10.1007/s40265-019-01165-2 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided 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 Article
Taieb, Julien
Jung, Andreas
Sartore-Bianchi, Andrea
Peeters, Marc
Seligmann, Jenny
Zaanan, Aziz
Burdon, Peter
Montagut, Clara
Laurent-Puig, Pierre
The Evolving Biomarker Landscape for Treatment Selection in Metastatic Colorectal Cancer
title The Evolving Biomarker Landscape for Treatment Selection in Metastatic Colorectal Cancer
title_full The Evolving Biomarker Landscape for Treatment Selection in Metastatic Colorectal Cancer
title_fullStr The Evolving Biomarker Landscape for Treatment Selection in Metastatic Colorectal Cancer
title_full_unstemmed The Evolving Biomarker Landscape for Treatment Selection in Metastatic Colorectal Cancer
title_short The Evolving Biomarker Landscape for Treatment Selection in Metastatic Colorectal Cancer
title_sort evolving biomarker landscape for treatment selection in metastatic colorectal cancer
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728290/
https://www.ncbi.nlm.nih.gov/pubmed/31347092
http://dx.doi.org/10.1007/s40265-019-01165-2
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