Beyond the implications of agnostic biomarkers and their targets in GI tumors, there remains a window for biomarkers that exhibit context-specific behavior, such as the role of Claudin 18.2 in gastric cancer or the unique EGFR dependency of hotspot mutations such as p.V600E in BRAF or p.G12C in KRAS in the setting of colorectal cancer (CRC). Here, BRAF is linked to colorectal cancer.