A 62-year-old man has a cecal adenocarcinoma with KRAS codon 12 mutation and no MLH1/MSH2 loss on IHC. Which is the most appropriate statement regarding targeted therapy selection?
- A KRAS mutation predicts resistance to anti-EGFR monoclonal antibodies (cetuximab, panitumumab) ✓
- B KRAS mutation predicts sensitivity to BRAF V600E inhibitors
- C KRAS mutation has no predictive value for anti-EGFR therapy in colorectal cancer
- D Proficient MMR status confers benefit from pembrolizumab
Correct answer: A. KRAS mutation predicts resistance to anti-EGFR monoclonal antibodies (cetuximab, panitumumab)
Explanation
Activating KRAS mutations (codons 12, 13, and NRAS codons) render the RAS-MAP kinase pathway constitutively active downstream of EGFR, so cetuximab or panitumumab targeting EGFR produce no benefit. MMR-deficient (MSI-H) tumors respond to PD-1 inhibitors; this tumor has proficient MMR so pembrolizumab benefit is not established. BRAF V600E inhibitors target a different downstream effector.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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