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Life sciences · Journal article
Frontiers in Pharmacology · September 21, 2026
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Background Overexpression human epidermal growth factor receptor 2 (HER-2) has been identified as a key oncogenic driver in metastatic colorectal cancer (mCRC), detected in between 2% and 5% of the overall mCRC population, with a higher prevalence identified in RAS/RAF/PI3KCA wild-type patients. Optimal targeted interventions are seldom administered to patients with HER2-positive mCRC due to the absence of definitive anti-HER2 therapeutic regimens in the refractory setting. As a result, for patients who have undergone multiple lines of therapy—particularly those with cetuximab resistance driven by ERBB2 amplification-mediated bypass activation—treatment strategies are frequently confined to best palliative care or participation in clinical trials. Case presentation This report demonstrates a case of multi-line refractory mCRC with high-level HER2 overexpression. Following multi-line treatment therapies, the patient was treated with a zanidatamab-based chemotherapy salvage regimen, leading to a partial response (PR) and an ongoing progression-free survival of approximately 10 months. Conclusion This case study highlights that the combination of zanidatamab with liposomal irinotecan and raltitrexed may provide an encouraging anti-tumor therapeutic option for mCRC patients with extremely high-level HER-2 overexpression and resistance to conventional anti-EGFR therapies. These findings offer valuable clinical insights into combining bispecific anti-HER2 targeted therapy with an optimized chemotherapy backbone, warranting further evaluation in prospective trials. Nevertheless, future prospective trials with larger cohorts are warranted to establish its survival benefits and universal applicability definitively.