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| Status |
Public on Jun 05, 2024 |
| Title |
Elucidating and Pharmacologically Targeting Master Regulators of Stem-like Breast Cancer Cell State |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
In many tumors, small subpopulations of stem-like cells can exist in drug-resistant states that are transient and epigenetically governed. Single-cell RNA sequencing provides transcriptional profiles for individual cells which, although sparse and noisy, may provide insight into how they are regulated and how they may be targeted. We took a systems-biology approach to analyzing stem-like cells in breast tumors and predicting how this drug-resistant subpopulation might be sensitized to treatment. Our analysis predicted that the anthelmintic albendazole would reprogram the stem-like population, and a subsequent sensitizing-then-kill experiment in triple negative breast cancer PDX mice revealed a synergistic relationship between albendazole and the first-line treatment, paclitaxel. These results are a proof of concept that it is possible to use, a systems biology approach to identify drugs that can reprogram cell-state, and that tumor subpopulations which have long been considered intractable may be forced into a sensitive state.
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| Overall design |
Patient-derived xenograft (PDX) models were generated using dissociated tumor cells obtained from a patient with triple-negative breast carcinoma. The mice (n=2/arm) were treated with paclitaxel, ivermectin, albendazole, and DMSO (control) for 15 days, and tumors were harvested 2 hours after administration of the last dose of vehicle or drug. Then, the prepared libraries using Human Tumor Dissociation Kit (Miltenyi) were sequenced on an Illumina Novaseq 6000.
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| Contributor(s) |
Worley J, Noh H, You D, Dela Cruz FS, Kung A, Califano A |
| Citation(s) |
38798673 |
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| Submission date |
Feb 28, 2023 |
| Last update date |
Jun 06, 2024 |
| Contact name |
Andrea Califano |
| E-mail(s) |
ac2248@cumc.columbia.edu
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| Organization name |
Columbia University
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| Department |
Systems Biology
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| Street address |
1130 St. Nicholas Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA939709 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE226329_RAW.tar |
369.3 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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