Sotorasib/Panitumumab Resistance May Be Linked to Genomic Alterations in KRAS G12C+ mCRC
Treatment resistance to sotorasib (Lumakras) plus panitumumab (Vectibix) in patients with KRAS G12C‑mutated metastatic colorectal cancer (mCRC) may stem from dysregulation of DNA methylation, RTK pathways, and KRAS amplifications.
The randomized, phase 3 CodeBreaK 300 trial evaluated the combination of sotorasib (Lumakras) and panitumumab (Vectibix) in patients with KRAS G12C‑mutated metastatic colorectal cancer. In a biomarker analysis of progression samples, treatment resistance was associated with dysregulation of DNA methylation, alterations in receptor tyrosine kinase (RTK) pathways, and KRAS amplifications, with additional emergent alterations in ERBB2, MET, and DNMT3A in a subset of patients.
Identifying genomic drivers of resistance informs future biomarker‑guided therapy design and may identify therapeutic targets to overcome or prevent resistance in KRAS G12C‑mutated metastatic colorectal cancer.
Evidence level: Állatkísérletes. Állatmodellben vizsgálták.
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