Somatic Biomarker Testing (Including Liquid Biopsy) for Targeted Treatment and Immunotherapy in Metastatic Colorectal Cancer (KRAS, NRAS, BRAF, MMR/MSI, HER2, and TMB)

The epidermal growth factor receptor (EGFR) is overexpressed in colorectal cancer (CRC). EGFR-targeted therapy combined with monoclonal antibodies cetuximab and panitumumab has shown a clear survival benefit in patients with metastatic CRC. However, this benefit depends on a lack of variants in certain genes in the signaling pathway downstream from the EGFR. It has been hypothesized that knowledge of tumor cell KRAS, NRAS, BRAF variant status might be used to predict nonresponse to anti-EGFR monoclonal antibody therapy. NTRK gene fusions, which are rare kinase fusion events, are a potential therapeutic target for CRC patients who may benefit from tropomysosin receptor kinase (TRK) inhibitor therapy. RET gene fusions, which are also rare, are a potential therapeutic target for CRC patients who may benefit from tyrosine kinase inhibitor therapy. More recently, human epidermal growth factor receptor 2 (HER2) testing to select patients for targeted therapy has been proposed. Typically, the evaluation of biomarker status requires tissue biopsy. Circulating tumor DNA or circulating tumor cell testing (also known as a liquid biopsy) is proposed as a non-invasive alternative.