ABSTRACT
Introduction
Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Although overall survival for CRC patients has improved with earlier screening, survival continues to vary substantially across stages. Also, while the introduction of targeted therapies, including VEGF and EGFR inhibitors, has contributed to improving survival, better tools are needed to optimize patient selection and maximize therapeutic benefits. Emerging biomarkers can be used to guide pharmacologic decision-making, as well as monitor treatment response, clarify the need for adjuvant therapies, and indicate early signs of recurrence. This is a narrative review examining the current and evolving use of predictive and prognostic biomarkers in colorectal cancer.
Areas covered
Areas covered include mutations of the MAPK (KRAS, BRAF) and HER2 pathways and their impacts on treatment decisions. In addition, novel methods for assessing tumor mutations and tracking treatment responses are examined.
Expert opinion
The standard of care pathway for staging, and treatment selection and surveillance, of CRC will expand to include novel biomarkers in the next 5 years. It is anticipated that these new biomarkers will assist in decision-making regarding selection of targeted therapies and, importantly, in risk stratification for treatment decisions in patients at high risk for recurrence.
Article highlights
Current recommendations suggest that most stage II CRC patients undergo surveillance for recurrent disease, rather than receiving adjuvant therapy. Given the percentage of these patients who later develop with metastases, there is a clear unmet clinical need for additional markers of high-risk disease.
Metastatic colon cancer with microsatellite instability responds to treatment with immune checkpoint inhibitors (PD-1 inhibitors and CTL4 inhibitors). Additional work is being conducted in patients with earlier stage disease.
BRAF mutations are a negative predictor of susceptibility to anti-EGFR therapy. While BRAF inhibitors have had limited efficacy in CRC, dual blockade with anti-EGFR agents and BRAF inhibitors have shown success.
The Consensus Molecular Subtype classification of CRCs may help guide therapeutic decision-making by improving prognostic and predictive categorization of tumors.
Beyond novel mechanistic biomarkers that guide treatment decisions, innovative methods of profiling CRC tumors like circulating tumor (ct)DNA have the potential to identify patients who require adjuvant therapy and assess disease responses across the treatment continuum.
Declaration of interest
SA Waldman is the Chair of the Scientific Advisory Board and member of the Board of Directors of, and AE Snook is a consultant for, Targeted Diagnostics and Therapeutics, Inc. which provided research funding that, in part, supported this work and has a license to commercialize inventions related to this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.