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Series GSE131980 Query DataSets for GSE131980
Status Public on Apr 08, 2020
Title Acquired resistance to combined BET and CDK4/6 inhibition in triple-negative breast cancer [Exome]
Organisms Homo sapiens; Mus musculus
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 Exome-seq of SUM159 breast cancer cell line treated 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
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 (2)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (23)
GSM3833304 Pre-1-B1
GSM3833305 C-1-C1
GSM3833306 T-1-D1
This SubSeries is part of SuperSeries:
GSE131986 Acquired resistance to combined BET and CDK4/6 inhibition in triple-negative breast cancer
BioProject PRJNA545506
SRA SRP199905

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Supplementary file Size Download File type/resource
GSE131980_CNV_report.xlsx 31.2 Mb (ftp)(http) XLSX
GSE131980_SNV-Indel-Phased.xlsx 119.1 Mb (ftp)(http) XLSX
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