Recent developments in the treatment of metastatic colorectal cancer

Over the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor re...

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Main Authors: Jonathan M. Loree, Scott Kopetz
Format: Article
Language:English
Published: SAGE Publishing 2017-08-01
Series:Therapeutic Advances in Medical Oncology
Online Access:https://doi.org/10.1177/1758834017714997
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author Jonathan M. Loree
Scott Kopetz
author_facet Jonathan M. Loree
Scott Kopetz
author_sort Jonathan M. Loree
collection DOAJ
description Over the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor receptor (EGFR) therapies and low-frequency mutations in RAS /tumor heterogeneity are gaining recognition as potential mechanisms of resistance. Despite this progress, the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy highlights our superficial understanding of this disease. Even with few new targeted agents receiving approval in CRC, the incorporation of next-generation sequencing into clinical decision making represents an important step forward. Biomarkers such as BRAF mutations, microsatellite instability, and HER2 amplification represent promising molecular aberrations with therapies in various stages of development, and highlight the importance of companion diagnostics in supporting targeted agents. In this review, we will discuss the importance of incorporating biomarkers into clinical decision making and regimen selection in CRC. We will particularly focus on the recent evidence suggesting an important role for tumor location in selecting first-line therapy, the importance of recent advances in biomarker development and molecular subtyping, as well as recently approved agents (regorafenib and TAS-102) and promising targeted agents that have the potential to change the standard of care.
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spelling doaj.art-ee17258c2a4a417b8a02e8e5882749d12022-12-22T01:55:46ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592017-08-01910.1177/1758834017714997Recent developments in the treatment of metastatic colorectal cancerJonathan M. LoreeScott KopetzOver the past decade there have been significant advances in the molecular characterization of colorectal cancer (CRC) that are driving treatment decisions. Expanded RAS testing beyond KRAS exon 2 was established as crucial for identifying patients who will respond to anti-epidermal growth factor receptor (EGFR) therapies and low-frequency mutations in RAS /tumor heterogeneity are gaining recognition as potential mechanisms of resistance. Despite this progress, the fact that we do not understand why left-sided but not right-sided tumors have improved outcomes following anti-EGFR therapy highlights our superficial understanding of this disease. Even with few new targeted agents receiving approval in CRC, the incorporation of next-generation sequencing into clinical decision making represents an important step forward. Biomarkers such as BRAF mutations, microsatellite instability, and HER2 amplification represent promising molecular aberrations with therapies in various stages of development, and highlight the importance of companion diagnostics in supporting targeted agents. In this review, we will discuss the importance of incorporating biomarkers into clinical decision making and regimen selection in CRC. We will particularly focus on the recent evidence suggesting an important role for tumor location in selecting first-line therapy, the importance of recent advances in biomarker development and molecular subtyping, as well as recently approved agents (regorafenib and TAS-102) and promising targeted agents that have the potential to change the standard of care.https://doi.org/10.1177/1758834017714997
spellingShingle Jonathan M. Loree
Scott Kopetz
Recent developments in the treatment of metastatic colorectal cancer
Therapeutic Advances in Medical Oncology
title Recent developments in the treatment of metastatic colorectal cancer
title_full Recent developments in the treatment of metastatic colorectal cancer
title_fullStr Recent developments in the treatment of metastatic colorectal cancer
title_full_unstemmed Recent developments in the treatment of metastatic colorectal cancer
title_short Recent developments in the treatment of metastatic colorectal cancer
title_sort recent developments in the treatment of metastatic colorectal cancer
url https://doi.org/10.1177/1758834017714997
work_keys_str_mv AT jonathanmloree recentdevelopmentsinthetreatmentofmetastaticcolorectalcancer
AT scottkopetz recentdevelopmentsinthetreatmentofmetastaticcolorectalcancer