Adaptation of redox metabolism in drug-tolerant persister cells is a vulnerability to prevent relapse in pancreatic cancer

Description

This dataset supports the study investigating metabolic adaptations in Pancreatic Ductal Adenocarcinoma (PDAC) related to therapeutic resistance and relapse. The research hypothesis is that drug-tolerant persister (DTP) cells survive chemotherapy by reprogramming their mitochondrial oxidative and redox metabolism, contributing to tumor relapse. Using preclinical PDAC mouse models (patient-derived xenografts and syngeneic allografts), the study measured mitochondrial and redox features of tumors during treatment-induced regression and relapse. Data include flow cytometry analyses of mitochondrial mass, membrane potential, ATP, reactive oxygen species (ROS) levels, antioxidant measurements, bulk RNA-sequencing, and RT-qPCR from tumor samples. Key findings reveal increased mitochondrial activity, elevated ATP and ROS levels, and upregulated antioxidant defenses in relapsed tumors. These metabolic adaptations likely support survival of DTP cells during minimal residual disease. The dataset also includes results showing that combined treatment with arsenic trioxide (a ROS inducer) and buthionine sulfoximine (a glutathione synthesis inhibitor) prevents tumor relapse in xenograft models. These data provide valuable insights into the metabolic vulnerabilities of pancreatic cancer persister cells and can be used to explore therapeutic strategies targeting redox metabolism to prevent relapse.

Institutions

• Aix-Marseille Universite

  Provence-Alpes-Côte d'Azu, Marseille

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