Cycling persister cells | Nature Reviews Cancer

Access through your institution Buy or subscribe Therapeutic resistance is not only driven by genetic evolution but often involves non-genetic adaptive mechanisms. As such, cancer cells can

escape therapeutic pressure by entering a reversible drug-tolerant persister state. The majority of these persister cells remain quiescent during drug treatment; however, a rare

subpopulation can resume the cell cycle, proliferate and facilitate tumour relapse. Yet, the factors that drive the appearance of this cycling persister subset are unknown and hard to assess

with bulk sequencing. To this end, Oren et al. developed a high-complexity lentiviral barcode library, called Watermelon, to simultaneously trace the clonal lineage, proliferation status

and transcriptional profile of individual cells during the course of drug treatment. Next, the authors applied their Watermelon system to characterize the mechanisms enabling persister cells

to withstand drug treatment and regain proliferative ability. Firstly, irreversible, mutational mechanisms that might account for the persister state were ruled out, as re-exposure of the

persister cell subset to osimertinib after a break in treatment led to both cycling and non-cycling persister subpopulations becoming sensitive to the targeted therapy again. This is a

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Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS:

* Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support REFERENCES ORIGINAL ARTICLE * Oren, Y. et al. Cycling cancer persister cells arise from lineages

with distinct programs. _Nature_ 596, 576–582 (2021) Article  CAS  Google Scholar  RELATED ARTICLE * Marine, J.-C. et al. Non-genetic mechanisms of therapeutic resistance in cancer. _Nat.

Rev. Cancer_ 20, 743–756 (2020) Article  CAS  Google Scholar  Download references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Nature Reviews Cancer http://www.nature.com/nrc/ Anna Dart

Authors * Anna Dart View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Anna Dart. RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Dart, A. Cycling persister cells. _Nat Rev Cancer_ 21, 683 (2021). https://doi.org/10.1038/s41568-021-00409-2 Download citation * Published:

14 September 2021 * Issue Date: November 2021 * DOI: https://doi.org/10.1038/s41568-021-00409-2 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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