Liquid biopsy to detect resistance mutations against anti-epidermal growth factor receptor therapy in metastatic colorectal cancer

Abstract

Colorectal cancer (CRC) is a major cause of mortality worldwide, associated with a steadily growing prevalence. Notably, the identification of KRAS , NRAS , and BRAF mutations has markedly improved targeted CRC therapy by affording treatments directed against the epidermal growth factor receptor (EGFR) and other anti-angiogenic therapies. However, the survival benefit conferred by these therapies remains variable and difficult to predict, owing to the high level of molecular heterogeneity among patients with CRC. Although classification into consensus molecular subtypes could optimize response prediction to targeted therapies, the acquisition of resistance mutations to targeted therapy is, in part, responsible for the lack of response in some patients. However, the acquisition of such mutations can induce challenges in clinical practice. The utility of liquid biopsy to detect resistance mutations against anti-EGFR therapy has recently been described. This approach may constitute a new standard in the decision algorithm for targeted CRC therapy.

Genomic and Transcriptomic Research in the Discovery and Application of Colorectal Cancer Circulating Markers

“…Among the other gene alterations potentially influencing the therapeutic decisions are NTRK fusions (after treatment with NTRK inhibitor, like entrectinib, for metastatic CRC) or ERBB2 amplification (possibly related to dual anti-HER-2 blockade) [45]. Mutations in ERBB2, MAP2K1, and NF1 and rearrangements of FGFR2, FGFR3, ALK, ROS1, NTRK1, and RET have recently emerged as novel biomarkers of the response to treatment with anti-EGFR monoclonal antibodies [46].…”

“…Even when the prediction almost ensures a positive response to a targeted therapy, the acquisition and clonal selection of mutations conferring resistance to targeted therapy can lead in some patients to severely reduced response or its absence [46]. According to Yi et al [50], the number of somatic mutations in ctDNA increased after the therapy and the rates of tracked mutations positively correlated with targeted therapy.…”