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Elucidating and Pharmacologically Targeting Master Regulators of Stem-like Breast Cancer Cell State

GSE226329 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2024/06/05 Platform GPL24676
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.
Published in
Identification and Pharmacological Targeting of Treatment-Resistant, Stem-like Breast Cancer Cells for Combination Therapy
Worley J, Noh H, You D et al. · bioRxiv : the preprint server for biology 2025 · PMID 38798673 · doi:10.1101/2023.11.08.562798
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Direct links to NCBI, no account and no request form: the whole study as GSE226329_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA939709 and SRA study SRP425002. Searching any of these in the dataset finder brings you back here.

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