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The role of cancer cell bioenergetics in dormancy and drug resistance

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Abstract

While anti-cancer drug treatments are often effective for the clinical management of cancer, these treatments frequently leave behind drug-tolerant persister cancer cells that can ultimately give rise to recurrent disease. Such persistent cancer cells can lie dormant for extended periods of time, going undetected by conventional clinical means. Understanding the mechanisms that such dormant cancer cells use to survive, and the mechanisms that drive emergence from dormancy, is critical to the development of improved therapeutic strategies to prevent and manage disease recurrence. Cancer cells often exhibit metabolic alterations compared to their non-transformed counterparts. An emerging body of evidence supports the notion that dormant cancer cells also have unique metabolic adaptations that may offer therapeutically targetable vulnerabilities. Herein, we review mechanisms through which cancer cells metabolically adapt to persist during drug treatments and develop drug resistance. We also highlight emerging therapeutic strategies to target dormant cancer cells via their metabolic features.

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Acknowledgements

This work was supported by the National Cancer Institute (R01CA211869, R01CA200994, R01CA262232, R01CA267691 to TWM; Dartmouth Cancer Center Support Grant P30CA023108).

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  1. Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Dartmouth Cancer Center, Lebanon, NH, USA

    Steven Tau & Todd W. Miller

  2. Dartmouth-Hitchcock Medical Center, One Medical Center Drive, HB-7936, Lebanon, NH 03756, USA

    Todd W. Miller

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Tau, S., Miller, T.W. The role of cancer cell bioenergetics in dormancy and drug resistance. Cancer Metastasis Rev 42, 87–98 (2023). https://doi.org/10.1007/s10555-023-10081-7

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