Abstract
The incorporation of novel biomarkers into therapy selection for patients with metastatic colorectal cancer (mcrc) has significantly improved outcomes. Optimal treatment planning now takes into account diverse characteristics of patients and their tumours to create personalized therapeutic plans. This review is split into two sections. In the first section, we review the prognostic and predictive significance of expanded RAS mutation testing, BRAF mutations, ERBB2 (her2) amplification, microsatellite instability (msi) and deficient mismatch repair (dmmr) protein, NTRK fusions, PIK3CA mutations, and met amplifications. The therapeutic implication of each of those biomarkers for personalizing therapies for each patient with mcrc is discussed. In the second section, we touch on testing methods and considerations of relevance to clinicians when they interpret companion diagnostics meant to guide therapy selection. The advantages and pitfalls of various methods are evaluated, and we also look at the potential of liquid biopsies and circulating tumour dna (ctdna) to change the landscape of therapeutic choice and biologic understanding of the disease. Routine testing for extended RAS, BRAF, dmmr or high msi, and NTRK fusions is necessary to determine the best sequencing of chemotherapy and biologic agents for patients with mcrc. Although next-generation sequencing and ctdna are increasingly being adopted, other techniques such as immunohistochemistry retain their relevance in detection of her2 amplification, NTRK fusions, and dmmr.
Highlights
DiscussionWe review the prognostic and predictive significance of expanded RAS mutation testing, BRAF mutations, ERBB2 (her2) amplification, microsatellite instability (msi) and deficient mismatch repair (dmmr) protein, NTRK fusions, PIK3CA mutations, and met amplifications
Summary Routine testing for extended RAS, BRAF, dmmr or high msi, and NTRK fusions is necessary to determine the best sequencing of chemotherapy and biologic agents for patients with mcrc
For 20 years, fluoropyrimidine doublet chemotherapy combined with either irinotecan or oxaliplatin has been the cornerstone of treatment for metastatic colorectal cancer in the first- and second-line settings[1,2]
Summary
We review the prognostic and predictive significance of expanded RAS mutation testing, BRAF mutations, ERBB2 (her2) amplification, microsatellite instability (msi) and deficient mismatch repair (dmmr) protein, NTRK fusions, PIK3CA mutations, and met amplifications. The therapeutic implication of each of those biomarkers for personalizing therapies for each patient with mcrc is discussed. We touch on testing methods and considerations of relevance to clinicians when they interpret companion diagnostics meant to guide therapy selection. Summary Routine testing for extended RAS, BRAF, dmmr or high msi, and NTRK fusions is necessary to determine the best sequencing of chemotherapy and biologic agents for patients with mcrc. Next-generation sequencing and ctdna are increasingly being adopted, other techniques such as immunohistochemistry retain their relevance in detection of her[2] amplification, NTRK fusions, and dmmr. Key Words Biomarkers, colorectal cancer, metastatic, next-generation sequencing, ctdna, anti-egfr
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