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Series GSE248450 Query DataSets for GSE248450
Status Public on May 17, 2024
Title Farnesyltransferase inhibition overcomes the adaptive resistance to targeted therapies in oncogene-addicted non-small cell lung cancer
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
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.
Overall design FUCCI-transduced HCC4006 subcloned cells were expanded in untreated (DMSO), osimertinib (1 µM) or osimertinib (1 µM) + tipifarnib (1 µM)-containing medium for 4, 20 and 12 days respectively. Drug-containing medium was changed 24h before sorting. Cells were dissociated by trypsinisation, recovered in FACS buffer (0,04% BSA in PBS) and kept on ice. G1 (red) and S/G2 (green) cells were sorted at 4°C using FACS Melody (BD Biosciences).
Contributor(s) Figarol S, Delahaye C, Cerapio Arroyo JP, Favre G, Calvayrac O
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Submission date Nov 22, 2023
Last update date May 17, 2024
Contact name Juan Pablo Cerapio
Organization name CRCT
Street address Av 2 Hubert Curien
City Toulouse
ZIP/Postal code 31000
Country France
Platforms (1)
GPL21697 NextSeq 550 (Homo sapiens)
Samples (6)
GSM7914538 DMSO-treated G1 HCC4006 cells
GSM7914539 Osimertinib-treated G1 HCC4006 cells
GSM7914540 Osimertinib+tipifarnib-treated G1 HCC4006 cells
BioProject PRJNA1044045

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Supplementary file Size Download File type/resource
GSE248450_HCC4006_all_processed_data.tsv.gz 254.9 Mb (ftp)(http) TSV
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Raw data are available in SRA

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