NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE131977 Query DataSets for GSE131977
Status Public on Apr 08, 2020
Title Acquired resistance to combined BET and CDK4/6 inhibition in triple-negative breast cancer [Barcode]
Organism Homo sapiens
Experiment type Genome variation profiling by high throughput sequencing
Summary BET inhibitors are promising therapeutic agents for the treatment of triple-negative breast cancer (TNBC), but the rapid emergence of resistance necessitates investigation of combination therapies and their effects on tumor evolution. Here, we show that palbociclib, a CDK4/6 inhibitor, and paclitaxel, a microtubule inhibitor, synergize with the BET inhibitor JQ1 in TNBC lines. High-complexity DNA barcoding and mathematical modeling indicate a high rate of de novo acquired resistance to these drugs relative to pre-existing resistance. We demonstrate that the combination of JQ1 and palbociclib induces cell division errors, which can increase the chance of developing aneuploidy. Characterizing acquired resistance to combination treatment at single cell level shows heterogeneous mechanisms including activation of G1-S and senescence pathways. Our results establish a rationale for further investigation of combined BET and CDK4/6 inhibition in TNBC and suggest novel mechanisms of action for these drugs, and new vulnerabilities in cells after emergence of resistance.
 
Overall design Barcode-seq of SUM159 breast cancer cell line treated in vivo and in vitro with JQ1, palbociclib, paclitaxel, and combinations
 
Contributor(s) Ge JY, Michor F, Polyak K
Citation(s) 32393766
Submission date May 30, 2019
Last update date May 19, 2020
Contact name Kornelia Polyak
E-mail(s) kornelia_polyak@dfci.harvard.edu
Phone 617-632-2106
Organization name Dana-Farber Cancer Institute
Department Medical Oncology
Lab Polyak
Street address 450 Brookline Ave
City Boston
State/province MA
ZIP/Postal code 02215
Country USA
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (174)
GSM3833076 JQ1Pal_2wk_1R
GSM3833077 JQ1Pal_2wk_2L
GSM3833078 JQ1Pal_2wk_3R
This SubSeries is part of SuperSeries:
GSE131986 Acquired resistance to combined BET and CDK4/6 inhibition in triple-negative breast cancer
Relations
BioProject PRJNA545507
SRA SRP199904

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE131977_RAW.tar 105.5 Mb (http)(custom) TAR (of TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap