Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine

Author:

Mouillet-Richard Sophie1ORCID,Cazelles Antoine1ORCID,Sroussi Marine1ORCID,Gallois Claire12ORCID,Taieb Julien12ORCID,Laurent-Puig Pierre13ORCID

Affiliation:

1. 1Team “Personalized medicine, pharmacogenomics, therapeutic optimization”, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Paris, France.

2. 2Institut du Cancer Paris CARPEM, APHP, Gastroenterology and Gastrointestinal Oncology Department, APHP.Centre - Université Paris Cité, Hôpital Européen G. Pompidou, Paris, France.

3. 3Institut du Cancer Paris CARPEM, APHP, Department of Biology, APHP.Centre - Université Paris Cité, Hôpital Européen G. Pompidou, Paris, France.

Abstract

Abstract Over the past decade, our understanding of the diversity of colorectal cancer has expanded significantly, raising hopes of tailoring treatments more precisely for individual patients. A key achievement in this direction was the establishment of the consensus molecular classification, particularly identifying the challenging consensus molecular subtype (CMS) CMS4 associated with poor prognosis. Because of its aggressive nature, extensive research is dedicated to the CMS4 subgroup. Recent years have unveiled molecular and microenvironmental features at the tissue level specific to CMS4 colorectal cancer. This has paved the way for mechanistic studies and the development of preclinical models. Simultaneously, efforts have been made to easily identify patients with CMS4 colorectal cancer. Reassessing clinical trial results through the CMS classification lens has improved our understanding of the therapeutic challenges linked to this subtype. Exploration of the biology of CMS4 colorectal cancer is yielding potential biomarkers and novel treatment approaches. This overview aims to provide insights into the clinico-biological characteristics of the CMS4 subgroup, the molecular pathways driving this subtype, and available diagnostic options. We also emphasize the therapeutic challenges associated with this subtype, offering potential explanations. Finally, we summarize the current tailored treatments for CMS4 colorectal cancer emerging from fundamental and preclinical studies.

Funder

SIRIC CARPEM

Fondation ARCAD

Labex Immuno-oncology

Association pour la Recherche sur le Cancer

Cancéropôle Ile de France

Fondation pour la Recherche Médicale

Institut National Du Cancer

Institut National de la Santé et de la Recherche Médicale

Publisher

American Association for Cancer Research (AACR)

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