Metabolic cell death (ferroptosis, cuproptosis, disulfidotosis, lysozyncosis, alkaliptosis) in cancer as a pharmacological basis for drug therapy

Resistance of tumor cells to cell death because of high level of aerobic glycolysis, compared with normal tissues, is a distinctive feature of cancer cells (Warburg effect). Recent studies have identified metabolism-related forms of cell death as unique types of regulated necrosis arising from imbalance in cellular metabolism. Necrosis plays an essential role in the development and homeostasis of nearly all multicellular organisms. In addition, dysregulation of cell death contributes to a wide range of pathological conditions. Historically, apoptosis was considered the principal programmed pathway of cell destruction, whereas necrosis was defined as an uncontrolled form of cell death. However, studies conducted over recent decades have revealed several important forms of regulated cell death that constitute part of the mechanisms of degenerative diseases, inflammatory disorders, and cancer. Growing understanding of these regulated, non-apoptotic cell death pathways opens new perspectives for therapeutic strategies. This article describes cell death mediated by regulated pathways, including necroptosis, ferroptosis, cuproptosis, autophagy-related cell death, lysosome-dependent cell death, and disulfidptosis. The mechanisms of metabolic cell death are discussed, and their potential in cancer therapy is explored. The complexity of metabolic cell death pathways is emphasized, and innovative ideas are proposed for understanding their therapeutic prospects in cancer treatment. The role of small-molecule inhibitors, regulatory pathways, and the prospects for anticancer drug development are also discussed.