What question did this study set out to answer?

The aim is to evaluate the effectiveness of OXPHOS inhibitors in preventing tumor growth originating from cancer stem cells in triple-negative breast cancer.

April 5, 2026

Abstract 945: Chemoprevention of triple-negative breast cancer originating from cancer stem cells using OXPHOS inhibitors

Key Points

The aim is to evaluate the effectiveness of OXPHOS inhibitors in preventing tumor growth originating from cancer stem cells in triple-negative breast cancer.
In vitro testing of OXPHOS inhibitors in cancer models derived from mammospheres.
Proteomic profiling to understand survival mechanisms of cancer stem cells.
Chemoprevention experiments using nude mice with prior exposure to OXPHOS inhibitors followed by injection of CSC-like cells.
Significant tumor growth inhibition was observed in inhibitor-treated groups compared to placebo.
Inhibition was more pronounced in tumors derived from cancer stem cells than in those from chemosensitive cells.
Mice treated with OXPHOS inhibitors showed slower tumor growth compared to control mice.

Abstract

Abstract We and other researchers have recently demonstrated in vitro that chemoresistant and stem-like triple-negative breast cancer cells preferentially obtain energy through mitochondrial oxidative phosphorylation (OXPHOS) compared to their chemosensitive counterparts, which undergo glycolysis. Proteomic profiling revealed several possible survival mechanisms for the resistant phenotype, including OXPHOS-associated pathways. Since metastasis and poor clinical prognosis are often associated with the dormant subset of slow-growing cancer stem cells (CSCs), we treated tumor models derived from mammospheres with pre-selected bactericidal antibiotics—OXPHOS inhibitors - AMX, FSS and others. Our results demonstrate significant inhibition of tumor growth in the inhibitor-treated groups compared to the placebo-treated group. Furthermore, this inhibition was more pronounced in tumors derived from CSCs than in tumors derived from chemosensitive cancer cells prone to glycolysis, further emphasizing the role of OXPHOS in CSCs. Since CSCs are often associated with a pool of chemoresistant OXPHOS-dependent cells, we conducted a chemoprevention experiment in which nude mice were given the above-mentioned inhibitors for several weeks, followed by injection with CSC-like cells (mammospheres) to create tumors. Our results showed a slowdown in tumor growth in the group of mice that had previously received these inhibitors, compared to mice that received a placebo. Thus, our experiments may be of interest for modeling the prevention of OXPHOS-dependent breast tumors. Citation Format: Esra Akkus, Cemile Uslu, Mert Güngör, Beyza Şimbil, Elif Uzun, Etna Abad, Alex Lyakhovich. Chemoprevention of triple-negative breast cancer originating from cancer stem cells using OXPHOS inhibitors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 945.

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