Sidedness (left vs right colon)
Where in the colon a tumour starts changes its biology and which drugs work. Left-sided tumours respond to EGFR antibodies; right-sided ones do not.
Right-sided (caecum to transverse) tumours are more often dMMR, BRAF-mutant, mucinous, and worse prognosis; left-sided (splenic flexure to rectum) are more often chromosomally unstable and EGFR-dependent. CALGB 80405, FIRE-3, and PARADIGM showed anti-EGFR benefit is confined to left-sided RAS wild-type disease. Embryologic origin (midgut vs hindgut) underlies the difference.
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