Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Cellular and Molecular Biology

Considering therapy-induced senescence as a mechanism of tumour dormancy contributing to disease recurrence

Summary

The capability of tumour cells to escape from therapy-induced senescence, as well as cell-non-autonomous functions of senescence, support the premise that senescence could serve as one pathway to tumour dormancy (among others that include quiescence and diapause) that is permissive for disease recurrence. Consequently, the pharmacologic targeting of senescent tumour cells could mitigate the risk for cancer resurgence, thereby enhancing the therapeutic efficacy of cancer chemotherapy.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Hypothetical model of the contribution of senescent tumour cells to tumour dormancy.

References

  1. Saleh T, Bloukh S, Carpenter VJ, Alwohoush E, Bakeer J, Darwish S, et al. Therapy-induced senescence: an “old” friend becomes the enemy. Cancers. 2020;12:822.

  2. Wang B, Demaria M. The quest to define and target cellular senescence in cancer. Cancer Res. 2021;81:6087–9.

    CAS  Article  Google Scholar 

  3. Zampetidis CP, Galanos P, Papantonis A, Zhu Y, Polyzou A, Karamitros T, et al. A recurrent chromosomal inversion suffices for driving escape from oncogene-induced senescence via subTAD reorganization. Mol Cell. 2021;81:4907–23.

  4. Dirac AMG, Bernards R. Reversal of senescence in mouse fibroblasts through lentiviral suppression of p53. J Biol Chem. 2003;278:11731–4.

    CAS  Article  Google Scholar 

  5. Duy C, Li M, Teater M, Meydan C, Garrett-Bakelman FE, Lee TC, et al. Chemotherapy induces senescence-like resilient cells capable of initiating AML recurrence. Cancer Discov. 2021;11:candisc.1375.2020.

  6. Risson E, Nobre AR, Maguer-Satta V, Aguirre-Ghiso JA. The current paradigm and challenges ahead for the dormancy of disseminated tumor cells. Nat Cancer. 2020;1:672–80.

  7. Santos-de-Frutos K, Djouder N. When dormancy fuels tumour relapse. Commun Biol. 2021;4:1–12.

    Article  Google Scholar 

  8. Muñoz DP, Yannone SM, Daemen A, Sun Y, Vakar-Lopez F, Kawahara M, et al. Targetable mechanisms driving immunoevasion of persistent senescent cells link chemotherapy-resistant cancer to aging. JCI Insight. 2019;4:e124716.

  9. Milanovic M, Fan DNY, Belenki D, Däbritz JH, Zhao Z, Yu Y, et al. Senescence-associated reprogramming promotes cancer stemness. Nature. 2018;553:96–100.

  10. Li Y, Kračun D, Dustin CM, El Massry M, Yuan S, Goossen CJ, et al. Forestalling age-impaired angiogenesis and blood flow by targeting NOX: interplay of NOX1, IL-6, and SASP in propagating cell senescence. Proc Natl Acad Sci USA. 2021;118:e2015666118.

  11. Aguirre-Ghiso JA. Translating the science of cancer dormancy to the clinic. Cancer Res. 2021;81:4673–5.

    CAS  Article  Google Scholar 

  12. Saleh T, Carpenter V, Tyutyunyk‐Massey L, Murray G, Leverson JD, Souers AJ, et al. Clearance of therapy‐induced senescent tumor cells by the senolytic ABT‐263 via interference with BCL‐X L ‐BAX Interaction. Mol Oncol. 2020;14:1–16.

  13. Carpenter VJ, Saleh T, Gewirtz DA. Senolytics for cancer therapy: is all that glitters really gold? Cancers. 2021;13:723.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

Research support relating to chemotherapy-induced senescence and senolytics in the Gewirtz laboratory is provided by the NIH/NCI through Grants CA 260819 and CA 239706.

Funding

None.

Author information

Authors and Affiliations

Authors

Contributions

TS and DAG contributed to the conceptualisation and writing of the manuscript.

Corresponding author

Correspondence to David A. Gewirtz.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Not applicable.

Consent to publish

Not applicable.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Saleh, T., Gewirtz, D.A. Considering therapy-induced senescence as a mechanism of tumour dormancy contributing to disease recurrence. Br J Cancer 126, 1363–1365 (2022). https://doi.org/10.1038/s41416-022-01787-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41416-022-01787-6

Search

Quick links