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Sotorasib Resistance in KRAS G12C-Mutant Invasive Mucinous Adenocarcinoma with Implications for VEGF-A

GSE295712 Homo sapiens Expression profiling by high throughput sequencing 5 samples Submitted 2025/05/02 Platform GPL28038
Summary
Invasive mucinous adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma with a poor prognosis. Compared to non-small cell lung cancer (NSCLCs), IMA more frequently harbors KRAS mutations in the order KRAS p.G12V, p.G12D, and p.G12C. This report describes a patient with KRAS p.G12C-mutant IMA treated with sotorasib. To date, no studies have investigated the therapeutic efficacy or resistance mechanisms of sotorasib in IMA. The patient was treated with carboplatin and pemetrexed, followed by sotorasib upon disease progression. While the primary lung lesions responded well, metastatic thoracic lymph node lesions continued to increase. A pathological autopsy was performed with the family’s consent to investigate potential resistance mechanisms. RNA sequencing and additional analyses revealed increased VEGF-A expression in metastatic lymph node lesions, suggesting a role in sotorasib resistance. These findings provide insights into the molecular mechanisms underlying treatment resistance in KRAS p.G12C-mutant IMA.
Published in
Sotorasib resistance in KRAS G12C-mutant invasive mucinous adenocarcinoma with implications for VEGF-A
Yanada H, Yoshida R, Kida R et al. · NPJ precision oncology 2025 · PMID 40419662 · doi:10.1038/s41698-025-00953-2
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Also filed as BioProject PRJNA1255652 and SRA study SRP581383. Searching any of these in the dataset finder brings you back here.

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