 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Sep 02, 2022 |
| Title |
Resistance to targeted therapies in the brain tumor microenvironment is not drive by genetic mutations |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| 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 |
Whole-exome sequencing performed on C2 and R2 cells growing in culture and R2 cells growing in the brain at resistance
|
| |
|
| Contributor(s) |
Adua SJ, Lopez-Giraldez F, Nguyen DX |
| Citation(s) |
36509758 |
| |
| Submission date |
May 21, 2021 |
| Last update date |
Dec 15, 2022 |
| Contact name |
Francesc Lopez |
| E-mail(s) |
francesc.lopez@yale.edu
|
| Organization name |
Yale University
|
| Department |
Department of Genetics
|
| Lab |
YCGA
|
| Street address |
P.O. Box 27386
|
| City |
West Haven |
| State/province |
CT |
| ZIP/Postal code |
06516 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA731911 |
| SRA |
SRP320874 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE174852_Sally_WES_n6.hg19_anno.xlsx |
137.1 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...