The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Cycling cancer persister cells arise from lineages with distinct programs
Open accessAbstract
Non-genetic mechanisms have recently emerged as important drivers of cancer therapy failure1, where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment2. Although most cancer persisters remain arrested in the presence of the drug, a rare subset can re-enter the cell cycle under constitutive drug treatment. Little is known about the non-genetic mechanisms that enable cancer persisters to maintain proliferative capacity in the presence of drugs. To study this rare, transiently resistant, proliferative persister population, we developed Watermelon, a high-complexity expressed barcode lentiviral library for simultaneous tracing of each cell’s clonal origin and proliferative and transcriptional states. Here we show that cycling and non-cycling persisters arise from different cell lineages with distinct transcriptional and metabolic programs. Upregulation of antioxidant gene programs and a metabolic shift to fatty acid oxidation are associated with persister proliferative capacity across multiple cancer types. Impeding oxidative stress or metabolic reprogramming alters the fraction of cycling persisters. In human tumours, programs associated with cycling persisters are induced in minimal residual disease in response to multiple targeted therapies. The Watermelon system enabled the identification of rare persister lineages that are preferentially poised to proliferate under drug pressure, thus exposing new vulnerabilities that can be targeted to delay or even prevent disease recurrence. Lineage tracing by barcoding of individual cells using a lentivirus library shows that cycling and non-cycling drug-tolerant persister cells in cancer arise from different lineages with distinct transcriptional and metabolic programs.
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Senescence and cancer — role and therapeutic opportunities
Schmitt, C. A., Wang, B., & Demaria, M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00668-4 · Cited by 794
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Jin, H., Wang, L., & Bernards, R. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00615-z · Cited by 503
Applications of single-cell RNA sequencing in drug discovery and development
Van de Sande, B., Lee, J. S., Mutasa-Gottgens, E., Naughton, B., Bacon, W., Manning, J., Wang, Y., Pollard, J., Mendez, M., Hill, J., et al. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00688-4 · Cited by 437
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Metadata
- Authors
- Oren, Y., Tsabar, M., Cuoco, M. S., Amir-Zilberstein, L., Cabanos, H. F., Hütter, J.-C., Hu, B., Thakore, P. I., Tabaka, M., Fulco, C. P., Colgan, W., Cuevas, B. M., Hurvitz, S. A., Slamon, D. J., Deik, A., Pierce, K. A., Clish, C., Hata, A. N., Zaganjor, E., Lahav, G., Politi, K., Brugge, J. S., & Regev, A.
- Venue
- Nature
- Published
- 2021-08-11
- Volume
- 596
- Issue
- 7873
- Pages
- 576-582
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3187309064
- Cited by
- 502
- References
- 36
- FWCI
- 27.23
- Type
- journal article
- Language
- en
- Open access
- green
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- Oren, Y., Tsabar, M., Cuoco, M. S., Amir-Zilberstein, L., Cabanos, H. F., Hütter, J.-C., Hu, B., Thakore, P. I., Tabaka, M., Fulco, C. P., Colgan, W., Cuevas, B. M., Hurvitz, S. A., Slamon, D. J., Deik, A., Pierce, K. A., Clish, C., Hata, A. N., Zaganjor, E., . . . Regev, A. (2021). Cycling cancer persister cells arise from lineages with distinct programs. Nature. https://doi.org/10.1038/s41586-021-03796-6
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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