OncoSKY Global shared a post on LinkedIn:
“ONCOSKY – Concept Clarity Series
Why Anti-EGFR Works Better in Distal (Left-Sided) Colon Cancer?
RAS WT is necessary — but NOT sufficient.
Right Colon (Midgut origin)
- Serrated pathway, CIMP-high
- Higher heterogeneity
- Pathway redundancy (MAPK bypass)
- Low AREG / EREG
- Immune & angiogenesis driven
EGFR is NOT the dominant driver
Limited benefit from anti-EGFR
Better with anti-VEGF (e.g., bevacizumab)
Left Colon (Hindgut origin)
- APC to TP53 chromosomal instability pathway
- More linear tumor evolution
- High AREG / EREG
- EGFR-dependent MAPK signaling
Tumor still depends on EGFR “switch”
Strong benefit from cetuximab / panitumumab
Better cytoreduction & OS in RAS WT disease
Trials: CALGB 80405, FIRE-3
Left-sided RAS WT to OS benefit
Right-sided RAS WT to No benefit / worse outcome
Take-Home:
Sidedness captures systems-level biology — not just anatomy.
Anti-EGFR works where oncogenic dependency exists.”
Other articles on Colon Cancer.