Targeting less common mutations in colorectal cancer
Sebastian Stintzing, MD
Charite University Hospital, Berlin, Germany
CodeBreaK 300: Sotorasib for KRAS G12C-mutated CRC
Filippo Pietrantonio, MD
Istituto Nazionale dei Tumori, Milan, Italy
Several genetic alterations play a role in the pathogenesis of mCRC, and testing of these biomarkers is an integral part of disease management for patients.
Most current international guidelines recommend testing patients with mCRC for KRAS, NRAS and BRAF mutations, and microsatellite instability (MSI).
However, with increased availability of novel targeted therapies, there is evidence to support wider biomarker testing and for this to include assessment of less frequently seen genetic changes, particularly in patients with chemotherapy-refractory CRC.
Testing recommendations of predictive genomic biomarkers in mCRC
*NGS panels used may enable rare alterations to be picked up, i.e. NTRK **Emerging biomarkers include HER2, MET, KRAS gene amplification, TGFα, EGFR mutations, and alterations in HER3, PI3KCA, and PTEN ±NTRK and HER2 are recommended for testing at relapse
Colorectal cancer NICE guideline [NG151]. Available at: https://www.nice.org.uk/guidance/ng151/chapter/Recommendations#molecular-biomarkers-to-guide-systemic-anti-cancer-therapy. Published January 2020. Last updated 15 December 2021.
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