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| Item Type: | Editorial |
|---|---|
| Title: | Persistence and/or senescence: not so lasting at last? |
| Creators Name: | Schmitt, C.A. |
| Abstract: | Therapy-exposed surviving cancer cells may have encountered profound epigenetic remodeling that renders these drug-tolerant persisters candidate drivers of particularly aggressive relapses. Typically presenting as slow-to-nongrowing cells, persisters are senescent or senescence-like cells. In this issue of Cancer Research, Ramponi and colleagues study mTOR/PI3K inhibitor–induced embryonic diapause–like arrest (DLA) as a model of persistence in lung cancer and melanoma cells and compare this persister condition with therapy-induced senescence in the same cells. The DLA phenotype recapitulated some but not all features attributed to senescent cells, lacking, for instance, an inflammatory secretome otherwise known as the senescence-associated secretory phenotype. A CRISPR dropout screen pointed to methyl group–providing one-carbon metabolism and further to H4K20me3-mediated repression of senescence-associated secretory phenotype–related IFN response genes selectively in DLA-like persister cells. Conversely, inhibition of H4K20-active KMT5B/C methyltransferases derepressed inflammatory programs and was toxic in DLA cells. These findings not only suggest exploitable vulnerabilities of DLA-like persister cells but also unveil general technical and conceptual challenges of cultured multipassage cell line–based persister studies. Collectively, the approach chosen and insights obtained will stimulate a productive scientific debate on senescence-like features and their reversibility across drug-tolerant persister cells. |
| Keywords: | Cellular Senescence, TOR Serine-Threonine Kinases, Animals |
| Source: | Cancer Research |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Volume: | 85 |
| Number: | 1 |
| Page Range: | 7-9 |
| Date: | 2 January 2025 |
| Official Publication: | https://doi.org/10.1158/0008-5472.CAN-24-3744 |
| PubMed: | View item in PubMed |
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