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Development of acquired resistance to sotorasib in NCI-H358 cell line in vitro

GSE277630 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2025/09/24 Platform GPL34284
Summary
NCI-H358 is a KRAS G12C-mutant non-small lung cancer cell line known to be sensitive to KRAS G12C-inhibitor sotorasib. Here, we aimed to develop sotorasib resistance in H358 and interrogate the resulting sotorasib-resistant cell line (H358-R). The H358-R cell line was created by continuous culturing of the H358 cells in sotorasib (250 nM) until cells grew readily under sotorasib pressure (approximately 2 months). We then performed RNA-seq of the resulting sotorasib-resistant cell line (H358-R) with and without sotorasib pressure, compared to the parental sensitive cell line control (H358). KRAS gene expression level was found to be increased in the sotorasib-resistant line compared with the parental cells, likely representing a mechanism of resistance. The increased KRAS expression level in the resistant cell line was maintained under sotorasib pressure.
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Also filed as BioProject PRJNA1162169 and SRA study SRP533255. Searching any of these in the dataset finder brings you back here.

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