Gemcitabine promotes autophagy and lysosomal function through ERK- and TFEB-dependent mechanisms.
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ABSTRACT: Gemcitabine is a first-line treatment agent for pancreatic ductal adenocarcinoma (PDAC). Contributing to its cytotoxicity, this chemotherapeutic agent is primarily a DNA replication inhibitor that also induces DNA damage. However, its therapeutic effects are limited owing to chemoresistance. Evidence in the literature points to a role for autophagy in restricting the efficacy of gemcitabine. Autophagy is a catabolic process in which intracellular components are delivered to degradative organelles lysosomes. Interfering with this process sensitizes PDAC cells to gemcitabine. It is consequently inferred that autophagy and lysosomal function need to be tightly regulated to maintain homeostasis and provide resistance to environmental stress, such as those imposed by chemotherapeutic drugs. How
SUBMITTER: Marchand B
PROVIDER: S-EPMC9902516 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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