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Non-lethal outcomes of engaging regulated cell death pathways in cancer

Abstract

Regulated cell death (RCD) is essential for successful systemic cancer therapy. Yet, the engagement of RCD pathways does not inevitably result in cell death. Instead, RCD pathways can take part in diverse biological processes if the cells survive. Consequently, these surviving cells, for which we propose the term ‘flatliners’, harbor important functions. These evolutionarily conserved responses can be exploited by cancer cells to promote their own survival and growth, with challenges and opportunities for cancer therapy.

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Fig. 1: Cell death pathways.
Fig. 2: Apoptosis induction and survival.
Fig. 3: ESCRT-mediated membrane repair of plasma membrane damage.
Fig. 4: Non-lethal outcomes for apoptosis-induced flatliners.
Fig. 5: Activation of NF-κB signaling.

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Acknowledgements

This work was supported by grants from the US National Institutes of Health (R35 CA231620) to D.R.G., the German Research Foundation (DFG; KA 4830/1-1), the Advanced Clinician Scientist Programm UMEA² (Medical Faculty, University of Duisburg-Essen) and the Federal Ministry of Education and Research (BMBF; 01EO2104) to H.K., the Swiss National Science Foundation Postdoc.Mobility Fellowship (P400PB_194393) to S.R., the US National Cancer Institute (T32CA272387) to J.J.P.S. and the American Lebanese Syrian Associated Charities (SJCRH). Figures were created with https://biorender.com.

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Kalkavan, H., Rühl, S., Shaw, J.J.P. et al. Non-lethal outcomes of engaging regulated cell death pathways in cancer. Nat Cancer 4, 795–806 (2023). https://doi.org/10.1038/s43018-023-00571-6

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