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  • Perspective
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Targeting therapy-persistent residual disease

Nature Cancer volume 5, pages 1298–1304 (2024)Cite this article

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Abstract

Disease relapse driven by acquired drug resistance limits the effectiveness of most systemic anti-cancer agents. Targeting persistent cancer cells in residual disease before relapse has emerged as a potential strategy for enhancing the efficacy and the durability of current therapies. However, barriers remain to implementing persister-directed approaches in the clinic. This Perspective discusses current preclinical and clinical complexities and outlines key steps toward the development of clinical strategies that target therapy-persistent residual disease.

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Fig. 1: Nongenetic sources of therapy-persistent RD.
Fig. 2: Framework for clinical evaluation of persister-directed therapies.

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Acknowledgements

A.N.H. was supported by US National Institutes of Health (NIH) R01 CA249291, P50 CA265826, the Break Through Cancer foundation and the Ludwig Center at Harvard. X.S. was supported by the QB3 Postdoc Entrepreneurship Fellowship. S.J.A. was supported by the Mark Foundation for Cancer Research ASPIRE Award. L.F.W. was supported by NIH R01 CA184984.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA

    Xiaoxiao Sun, Lani F. Wu & Steven J. Altschuler

  2. Massachusetts General Hospital Cancer Center, Boston, MA, USA

    Aaron N. Hata

  3. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Aaron N. Hata

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  1. Xiaoxiao Sun
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  2. Lani F. Wu
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Correspondence to Lani F. Wu, Steven J. Altschuler or Aaron N. Hata.

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Competing interests

A.N.H. has received grants and/or research support from Amgen, BridgeBio, Bristol Myers Squibb, C4 Therapeutics, Eli Lilly, Novartis, Nuvalent, Pfizer and Scorpion Therapeutics and has served as a compensated consultant for Amgen, Engine Biosciences, Nuvalent, Oncovalent, Pfizer, TigaTx and Tolremo Therapeutics. X.S., L.F.W. and S.J.A. declare no competing interests.

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Sun, X., Wu, L.F., Altschuler, S.J. et al. Targeting therapy-persistent residual disease. Nat Cancer 5, 1298–1304 (2024). https://doi.org/10.1038/s43018-024-00819-9

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