Transition between cell states of sensitivity reveals molecular vulnerability of drug-tolerant cells.

ABSTRACT: Drug-tolerant cells to pro-apoptotic treatments exhibit transient resistance to subsequent challenges, which can be sustained via transcriptional and translational regulations. Although persister cells have been described in other cell death modalities, how they respond to subsequent treatments that are different from the one they originate from remains less explored. Here we show that drug-tolerant cells to pro-apoptotic treatments exhibit a reduced capacity to activate caspase-8, as well as higher levels of RIPK3 protein expression. As this apoptosis-tolerant cell state exhibits features of vulnerability to necroptosis, we show that alternating from apoptotic to necroptotic treatments increases cell response compared to drug holiday or sustained treatment. To gain insights on these trans

SUBMITTER: Peyre L 

PROVIDER: S-EPMC12673137 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature