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Series GSE174850 Query DataSets for GSE174850
Status Public on Sep 02, 2022
Title The brain tumor microenvironment primes metastatic cells for resistance to targeted therapies
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The brain is a major sanctuary site for metastatic lung cancer cells that evade systemic therapies. We performed pharmacological, biological, and molecular studies to identify the functional link between drug resistance and central nervous system (CNS) relapse in late-stage EGFR mutant non-small cell lung cancer, which frequently progresses in the brain even when treated with the brain penetrant EGFR inhibitor osimertinib. Despite widespread osimertinib distribution in vivo, the brain microvascular tumor microenvironment (TME) is associated with the persistence of malignant cell sub-populations which are poised to further proliferate in the brain as osimertinib-resistant lesions over time. Cellular and molecular features of this poised state are commonly regulated through RhoA signaling, which potentiates the outgrowth of disseminated tumor cells on osimertinib treatment, preferentially in response to extracellular laminin and in the brain. Thus, we identify pre-existing and adaptive features of metastatic and drug resistant cancer cells, which are enhanced by RhoA and the brain TME during the evolution of osimertinib resistant disease.
Overall design Species specific RNA-seq performed in control (C2) and resistant (R2) human cell populations growing in mouse brain when treated with vehicle or osimertinib. There are 6 in vivo sample groups each with 3-4 reps. The same control and resistant cell populations growing in culture and treated with vehicle or osimertinib were also sent for sequencing (3 reps each).
Contributor(s) Adua SJ, Liu Z, Lopez-Giraldez F, Nguyen DX
Citation(s) 36509758
Submission date May 21, 2021
Last update date Dec 15, 2022
Contact name Francesc Lopez
Organization name Yale University
Department Department of Genetics
Street address P.O. Box 27386
City West Haven
State/province CT
ZIP/Postal code 06516
Country USA
Platforms (2)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
GPL22245 Illumina HiSeq 2500 (Homo sapiens; Mus musculus)
Samples (35)
GSM5329232 SA1: Cv2D_rep1 RNA-seq
GSM5329233 SA2: Cv2D_rep2 RNA-seq
GSM5329234 SA3: Cv2D_rep3 RNA-seq
BioProject PRJNA731909
SRA SRP320872

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Supplementary file Size Download File type/resource
GSE174850_hgmastersheetPruned.x_pseudogene.rpkm.txt.gz 4.0 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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