Metabolic cell death in cancer: mechanisms and therapeutic potential.

A defining hallmark of malignant tumours lies in their pronounced resistance to programmed cell death mechanisms. This intrinsic resilience enables cancer cells to circumvent physiological clearance, thereby sustaining unchecked proliferation and survival. Emerging research has revealed that metabolic dysregulation can precipitate a distinctive form of programmed cell death, termed metabolism-linked regulated cell death (RCD), establishing it as a novel paradigm of cellular self-elimination. This systematic review provides an in-depth analysis of the molecular mechanisms orchestrating various metabolic cell death modalities, including pyroptosis, immunogenic cell death (ICD), necroptosis, ferroptosis, cuproptosis, disulfidptosis, lysozincrosis, alkaliptosis, and methuosis. Furthermore, it critically evaluates their therapeutic potential in oncology. By elucidating the intricate interplay among these signalling cascades, this review describes innovative precision medicine strategies that harness metabolism-driven cell death for targeted cancer interventions.