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Review
. 2021 Sep 7;13(18):4506.
doi: 10.3390/cancers13184506.

Tackling Refractory Metastatic Colorectal Cancer: Future Perspectives

Nicola Personeni  1   2 , Valeria Smiroldo  2 , Emilio Francesco Giunta  3 , Maria Giuseppina Prete  1   2 , Lorenza Rimassa  1   2 , Giacomo Bregni  4 , Francesco Sclafani  4
Affiliations
Review

Tackling Refractory Metastatic Colorectal Cancer: Future Perspectives

Nicola Personeni et al. Cancers (Basel). .

Abstract

Substantial improvements have characterized the systemic treatment of metastatic colorectal cancer (mCRC) over the past 20 years. Besides strong evidence that supports the use of RAS and BRAF status as prognostic and predictive indicators of disease and response, novel technologies have made possible the incorporation of emerging biomarkers for the management of mCRC. On one hand, the discovery of point mutations, amplifications, fusions, and gene expression profiles highlights the genomic and dynamic complexity of CRC. On the other, such discoveries are leading to newer biomarker-driven strategies that add to existing anti-epidermal growth factor receptor (EGFR) and anti-angiogenic approaches. In addition, the availability of a wide molecular profiling has relevant implications for patient prognosis and treatment benefits. Here, we will review the molecular underpinnings and clinical data supporting novel targeted treatments under development for refractory mCRC harboring BRAF mutations, KRAS G12C mutations, HER2 amplification, and less common molecular alterations, such as the re-arrangements of NTRK, ALK, and ROS1. Additionally, we will discuss novel strategies driving the rechallenge of EGFR antibodies and the incorporation of newer anti-angiogenic agents in the therapeutic armamentarium.

Keywords: biomarker-driven strategies; colorectal cancer; metastatic; molecular characterization; refractory; targeted agents.

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Conflict of interest statement

N.P. reports receiving consulting fees from Amgen, Merck Serono, Servier; lectures fees from AbbVie, Gilead, Lilly, Sanofi; travel expenses from Amgen, ArQule; and institutional research funding from Basilea, Merck Serono, Servier. EFG reports receiving personal fees from Novartis. LR reports receiving consulting fees from Amgen, ArQule, AstraZeneca, Basilea, Bayer, BMS, Celgene, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Lilly, MSD, Nerviano Medical Sciences, Roche, Sanofi, Servier, Zymeworks; lecture fees from AbbVie, Amgen, Bayer, Eisai, Gilead, Incyte, Ipsen, Lilly, Merck Serono, Roche, Sanofi; travel expenses from Ipsen; and institutional research funding from Agios, ARMO BioSciences, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks. FS reports receiving consulting fees from Amal Therapeutics, Bayer; travel expenses from Bayer, Lilly; institutional research funding from Amgen, AstraZeneca, Bayer, BMS, Roche, Sanofi; and leadership role as Co-Chair EORTC Colon Cancer Task Force. There are no other personal or financial conflicts of interest to disclose.

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