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Series GSE193258

Query DataSets for GSE193258

Status

Public on Apr 06, 2022

Title

The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells [RNA-seq]

Organism

Experiment type

Expression profiling by high throughput sequencing

Summary

Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, an irreversible EGFR-TKI, are important treatments for non-small cell lung cancer with EGFR-TKI sensitizing or EGFR T790M resistance mutations. Whilst patients treated with osimertinib show clinical benefit, disease progression and drug resistance are common. Emergence of de novo acquired resistance from a drug tolerant persister (DTP) cell population is one mechanism proposed to explain progression on osimertinib and other targeted cancer therapies. Here we profiled osimertinib DTPs using RNA-seq, ChIP-seq, and ATAC-seq to characterize the features of these cells and performed drug screens to identify therapeutic opportunities.

Overall design

The NSCLC EGFR mutant cell lines (PC9, NCI-H1975, HCC827, and HCC2935) were treated with 500 nM osimertinib for 21 days (osimertinib DTPs). Cells were either harvested immediately or washed 2x with PBS and then replaced with drug-free media for a further 24 hrs. (short washout), or for a longer time-point (long washout) until exponential cell proliferation resumed (PC9: 7 days; NCI-H1975: 3 days; HCC827: 4 days; HCC2935: 10 days) and then harvested. In parallel, parental cell lines were grown in drug-free media for 21 days then treated with 500 nM osimertinib for 24 hrs. (osimertinib acute) or vehicle DMSO control for 24 hrs. (DMSO control). Experiment was done using biological triplicates. There are 60 total RNA-seq samples.

Contributor(s)

Criscione SW, Martin MJ, Oien DB, Miragaia R, Gorthi A, Zhang J, Chen H, Karl D, Mendler K, Markovets A, Gagrica S, Delpuech O, Dry JR, Drew L, Yao Y, Smith PD

Citation(s)

35351890, 36575215, 36969743

Submission date

Jan 07, 2022

Last update date

Apr 25, 2023

Contact name

Paul D Smith

Organization name

AstraZeneca

Street address

AstraZeneca CRUK Cambridge Institute, Robinson Way

City

Cambridge

ZIP/Postal code

CB20RE

Country

United Kingdom

Platforms (1)

Illumina HiSeq 4000 (Homo sapiens)

Samples (60)

More...

GSM5777996	H1975_DMSO_1 [RNA-seq]
GSM5777997	H1975_DMSO_2 [RNA-seq]
GSM5777998	H1975_DMSO_3 [RNA-seq]

GSM5777999	H1975_long_washout_72h_1 [RNA-seq]
GSM5778000	H1975_long_washout_72h_2 [RNA-seq]
GSM5778001	H1975_long_washout_72h_3 [RNA-seq]
GSM5778002	H1975_osi_acute_1 [RNA-seq]
GSM5778003	H1975_osi_acute_2 [RNA-seq]
GSM5778004	H1975_osi_acute_3 [RNA-seq]
GSM5778005	H1975_osi_DTP_1 [RNA-seq]
GSM5778006	H1975_osi_DTP_2 [RNA-seq]
GSM5778007	H1975_osi_DTP_3 [RNA-seq]
GSM5778008	H1975_short_washout_1 [RNA-seq]
GSM5778009	H1975_short_washout_2 [RNA-seq]
GSM5778010	H1975_short_washout_3 [RNA-seq]
GSM5778011	HCC2935_DMSO_1 [RNA-seq]
GSM5778012	HCC2935_DMSO_2 [RNA-seq]
GSM5778013	HCC2935_DMSO_3 [RNA-seq]
GSM5778014	HCC2935_long_washout_10d_1 [RNA-seq]
GSM5778015	HCC2935_long_washout_10d_2 [RNA-seq]
GSM5778016	HCC2935_long_washout_10d_3 [RNA-seq]
GSM5778017	HCC2935_osi_acute_1 [RNA-seq]
GSM5778018	HCC2935_osi_acute_2 [RNA-seq]
GSM5778019	HCC2935_osi_acute_3 [RNA-seq]
GSM5778020	HCC2935_osi_DTP_1 [RNA-seq]
GSM5778021	HCC2935_osi_DTP_2 [RNA-seq]
GSM5778022	HCC2935_osi_DTP_3 [RNA-seq]
GSM5778023	HCC2935_short_washout_1 [RNA-seq]
GSM5778024	HCC2935_short_washout_2 [RNA-seq]
GSM5778025	HCC2935_short_washout_3 [RNA-seq]
GSM5778026	HCC827_DMSO_1 [RNA-seq]
GSM5778027	HCC827_DMSO_2 [RNA-seq]
GSM5778028	HCC827_DMSO_3 [RNA-seq]
GSM5778029	HCC827_long_washout_96h_1 [RNA-seq]
GSM5778030	HCC827_long_washout_96h_2 [RNA-seq]
GSM5778031	HCC827_long_washout_96h_3 [RNA-seq]
GSM5778032	HCC827_osi_acute_1 [RNA-seq]
GSM5778033	HCC827_osi_acute_2 [RNA-seq]
GSM5778034	HCC827_osi_acute_3 [RNA-seq]
GSM5778035	HCC827_osi_DTP_1 [RNA-seq]
GSM5778036	HCC827_osi_DTP_2 [RNA-seq]
GSM5778037	HCC827_osi_DTP_3 [RNA-seq]
GSM5778038	HCC827_short_washout_1 [RNA-seq]
GSM5778039	HCC827_short_washout_2 [RNA-seq]
GSM5778040	HCC827_short_washout_3 [RNA-seq]
GSM5778041	PC9_DMSO_1 [RNA-seq]
GSM5778042	PC9_DMSO_2 [RNA-seq]
GSM5778043	PC9_DMSO_3 [RNA-seq]
GSM5778044	PC9_long_washout_7d_1 [RNA-seq]
GSM5778045	PC9_long_washout_7d_2 [RNA-seq]
GSM5778046	PC9_long_washout_7d_3 [RNA-seq]
GSM5778047	PC9_osi_acute_1 [RNA-seq]
GSM5778048	PC9_osi_acute_2 [RNA-seq]
GSM5778049	PC9_osi_acute_3 [RNA-seq]
GSM5778050	PC9_osi_DTP_1 [RNA-seq]
GSM5778051	PC9_osi_DTP_2 [RNA-seq]
GSM5778052	PC9_osi_DTP_3 [RNA-seq]
GSM5778053	PC9_short_washout_1 [RNA-seq]
GSM5778054	PC9_short_washout_2 [RNA-seq]
GSM5778055	PC9_short_washout_3 [RNA-seq]

This SubSeries is part of SuperSeries:

The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells

Relations

BioProject

Download family	Format
SOFT formatted family file(s)	SOFT
MINiML formatted family file(s)	MINiML
Series Matrix File(s)	TXT

Supplementary file	Size	Download	File type/resource
GSE193258_RNAseq_estimated_counts.tsv.gz	8.0 Mb	(ftp)(http)	TSV
GSE193258_RNAseq_log2TPM_abundance.tsv.gz	8.0 Mb	(ftp)(http)	TSV
SRA Run Selector
Raw data are available in SRA
Processed data are available on Series record

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