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cmLumiOpto gene therapy in combination with chemotherapy to treat triple negative breast cancer.

GSE305990 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2026/01/12 Platform GPL21273
Summary
Triple-negative breast cancer (TNBC) is aggressive, resistant to chemotherapy, and prone to recurrence. While PARP inhibitors (PARPi) help some patients, most do not respond. We developed a novel therapy combining mitochondria-targeted luminoptogenetics (cmLumiOpto) with PARPi to enhance treatment. Delivered via an anti-CD276 monoclonal antibody-conjugated exosome-AAV (mAb-Exo-AAV), cmLumiOpto disrupts mitochondrial membrane potential, inducing cancer cell death. In vitro, the combination increased cytotoxicity; in vivo, it reduced tumor burden by 95–100%, suppressed xenograft growth, and blocked metastasis in TNBC models. Mechanistic studies showed mitochondrial depolarization, DNA damage, cytokine release, and immune infiltration, highlighting a promising strategy for TNBC therapy. The mechanism of action was further explained through bulk RNA sequencing post-treatment. These findings highlight the therapeutic potential of our cmLumiOpto gene therapy for treatment of triple negative breast cancers.
Published in
Combine mitochondrial-targeted gene therapy and chemotherapy to treat triple-negative breast cancer
Varadkar T, Zhou ZZ, Zhang J et al. · Journal of experimental & clinical cancer research : CR 2025 · PMID 41462289 · doi:10.1186/s13046-025-03572-8
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Direct links to NCBI, no account and no request form: the whole study as GSE305990_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 PRJNA1308851 and SRA study SRP610488. Searching any of these in the dataset finder brings you back here.

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