Molecular subtypes and the evolution of treatment management in metastatic colorectal cancer

• Published in: Therapeutic Advances in Medical Oncology Vol. 12; p. 1758835920936089
• Main Authors: Martini, Giulia, Dienstmann, Rodrigo, Ros, Javier, Baraibar, Iosune, Cuadra-Urteaga, Jose Luis, Salva, Francesc, Ciardiello, Davide, Mulet, Nuria, Argiles, Guillem, Tabernero, Josep, Elez, Elena
• Format: Book Review Journal Article
• Language: English
• Published: London, England SAGE Publications 2020; Sage Publications Ltd; SAGE Publishing
• Subjects: Biopsy; Chemotherapy; Clonal selection; Colorectal cancer; Colorectal carcinoma; DNA damage; DNA repair; Epidermal growth factor; Epidermal growth factor receptors; ErbB-2 protein; Genomic analysis; Metastases; Metastasis; Review; colorectal cancer; RAS; biomarkers; EGFR; molecular classification
• ISSN: 1758-8359; 1758-8340; 1758-8359
• DOI: 10.1177/1758835920936089

Colorectal cancer (CRC) is a heterogeneous disease representing a therapeutic challenge, which is further complicated by the common occurrence of several molecular alterations that confer resistance to standard chemotherapy and targeted agents. Mechanisms of resistance have been identified at multiple levels in the epidermal growth factor receptor (EGFR) pathway, including mutations in KRAS, NRAS, and BRAFV600E, and in the HER2 and MET receptors. These alterations represent oncogenic drivers that may co-exist in the same tumor with other primary and acquired alterations via a clonal selection process. Other molecular alterations include DNA damage repair mechanisms and rare kinase fusions, potentially offering a rationale for new therapeutic strategies. In recent years, genomic analysis has been expanded by a more complex study of epigenomic, transcriptomic, and microenvironment features. The Consensus Molecular Subtype (CMS) classification describes four CRC subtypes with distinct biological characteristics that show prognostic and potential predictive value in the clinical setting. Here, we review the panorama of actionable targets in CRC, and the developments in more recent molecular tests, such as liquid biopsy analysis, which are increasingly offering clinicians a means of ensuring optimal tailored treatments for patients with metastatic CRC according to their evolving molecular profile and treatment history.