Dying on Their Own Terms: Ferroptosis, Cuproptosis, and the New Wave of Non Apoptotic Cell Death Reshaping Cancer Biology and Therapy

AbstractNon apoptotic cell death programs particularly ferroptosis and cuproptosis are transforming how we understand cancer survival and treatment resistance. These pathways reveal new molecular vulnerabilities that go beyond the traditional focus on apoptosis, offering novel therapeutic angles for aggressive and treatment refractory cancers. This Research Topic aims to gather studies exploring the mechanisms, metabolic regulation, and translational implications of these emerging death programs within the framework of cancer cell biology. We are especially interested in how lipid metabolism reprogramming drives ferroptotic sensitivity, how copper dependent mitochondrial stress leads to cuproptosis, and how these mechanisms connect with tumour signalling and progression. By combining mechanistic cell biology with multi-omics approaches such as transcriptomics, proteomics, single cell sequencing, and spatial transcriptomics, this collection seeks to bridge discovery with clinical translation and inspire next generation strategies for cancer therapy.ScopeCancer cells manage to grow even under stress, avoiding the signals that normally trigger their death. Resistance to apoptosis is one of the main reasons why tumours recur and persist after treatment. To overcome this, researchers are turning their attention to other, less explored forms of regulated cell death that many cancer cells have yet to develop defences against. Ferroptosis arises when iron dependent lipid peroxidation overwhelms antioxidant defences, while cuproptosis is fuelled by copper overload that disrupts mitochondrial metabolism. Each is tightly linked to metabolic rewiring and core signalling networks that sit at the heart of cancer cell biology.This Research Topic focuses on how ferroptosis, cuproptosis, and related programs influence tumour behaviour, therapeutic response, and disease outcome. We encourage contributions that combine multi-omics analyses, including transcriptomic, proteomic, single cell, and spatial data with experimental validation to reveal new biomarkers and regulators of these pathways. Studies that connect these mechanisms to cellular metabolism, redox balance, and immune contexture are particularly welcome.We are interested in research that defines the molecular drivers of ferroptosis and cuproptosis in cancer, explores how lipid metabolism reprogramming contributes to non-apoptotic death sensitivity, and investigates how key signalling pathways (PI3K/AKT/mTOR, MAPK, p53) intersect with these processes. Work identifying biomarkers through integrative multi-omics, studying non?coding RNAs and epigenetic regulation, or proposing therapeutic strategies using ferroptosis inducers, copper ionophores, and combination regimens is also encouraged.Submissions should present experimental or biological evidence with clear relevance to cell biology. Purely computational analyses without functional validation fall outside the scope. Topic editors: Qin Xie, Cheng Zeng, Pei Shengbin Source: https://www.frontiersin.org/research-topics/82211/dying-on-their-own-terms-ferroptosis-cuproptosis-and-the-new-wave-of-non-apoptotic-cell-death-reshaping-cancer-biology-and-therapy