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Farnesyltransferase inhibition overcomes the adaptive resistance to targeted therapies in oncogene-addicted non-small cell lung cancer

GSE248450 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2024/05/17 Platform GPL21697
Summary
Drug-tolerance has emerged as one of the major non-genetic adaptive processes driving resistance to targeted therapy (TT) in non-small cell lung cancer (NSCLC). However, the kinetics and sequence of molecular events governing this adaptive response remain poorly understood. Here, we used the FUCCI (fluorescence ubiquitination cell cycle indicator) system to perform real-time monitoring of the cell cycle dynamics the EGFR-mutant NSCLC cell line HCC4006, which was previously subcloned to minimize the presence of potential pre-existing resistant cells. We performed scRNAseq on G1 (red) and S/G2 (green) cells sorted from untreated (DMSO), osimertinib-treated and osimertinib+tipifarnib-treated cells to identify molecular mechanisms implicated in the adaptive response to TT and the sensitivity of drug-tolerant cells to tipifarnib.
Published in
Farnesyltransferase inhibition overcomes oncogene-addicted non-small cell lung cancer adaptive resistance to targeted therapies
Figarol S, Delahaye C, Gence R et al. · Nature communications 2024 · PMID 38937474 · doi:10.1038/s41467-024-49360-4
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Also filed as BioProject PRJNA1044045 and SRA study SRP473707. Searching any of these in the dataset finder brings you back here.

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