Application and potential of the tumor microenvironment, ferroptosis, cuproptosis, and disulfidptosis in cancer treatment and monitoring

Abstract

The interplay between the tumor microenvironment and metabolic cell death pathways has emerged as a critical focus in contemporary cancer research. This comprehensive review examines the mechanistic interactions between these processes and evaluates their therapeutic and diagnostic implications in cancer management. Following Hanahan and Weinberg's seminal characterization of cancer hallmarks in 2011, substantial experimental and clinical evidence has accumulated, expanding our understanding of tumor biology. This review specifically addresses several key aspects: metabolic perturbations within the TME and their interactions with ferroptosis, cuproptosis, and disulfidptosis pathways; therapeutic agents and combinatorial approaches targeting these distinct metabolic cell death mechanisms; advanced delivery systems, particularly nanocarrier-based platforms, for enhancing metabolic cell death-inducing therapeutic strategies. It also points out the limitations of various therapeutic approaches that induce metabolic death in tumor cells, and predicts the directions that can be focused on exploring in the future.