Before starting cetuximab for metastatic colorectal cancer, tumour tissue must be tested for which biomarker, because its mutation predicts complete lack of benefit?

• A BCR-ABL fusion transcript
• B HER2 amplification
• C Microsatellite instability
• D KRAS codon 12 and 13 mutation status ✓

Explanation

Cetuximab blocks the extracellular domain of EGFR, but downstream constitutive activation by a KRAS mutation makes upstream blockade futile. Only RAS wild-type tumours respond, so KRAS exon 2 (codons 12 and 13) testing is mandatory before use in colorectal cancer. Microsatellite instability predicts response to PD-1 inhibitors, HER2 amplification predicts trastuzumab benefit, and BCR-ABL defines imatinib sensitivity in CML.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.