Abstract
This review examine the nematode Caenorhabditis elegans as a powerful model for cancer research, moving beyond its well-established utility in dissecting conserved genetic pathways. Its true strength may lie in modeling the intricate interplay between dysregulated metabolism and oxidative stress. This review first discusses how C. elegans provides a whole-organism system to study the causal links between metabolic overload, the production of reactive oxygen species (ROS), and the activation of conserved detoxification pathways. The discussion then shifts to the Warburg effect, presenting the worm's unique rhodoquinone-dependent anaerobic metabolism as an evolutionary control experiment that offers a non-canonical framework for understanding the functional roles of lactate in the tumor microenvironment. Finally, this review examines the cell nucleus as an active sensor of stress, discussing how oxidative stress triggers the structural reorganization, from global chromatin remodeling to the formation of stress-induced biomolecular condensates. It is concluded that C. elegans offers an excellent platform to progress from studying isolated cancer-related pathways toward an integrated understanding of the metabolic and environmental stress that drives tumorigenesis.