Apoptosis最新文献

{"title":"Apolipoprotein A1 attenuates epirubicin-induced cardiotoxicity with GPX4-linked ferroptosis-defense modulation","authors":"Guoli Yang,&nbsp;Qin Duan,&nbsp;Kangla Liao,&nbsp;Bi Huang,&nbsp;Qian Dong","doi":"10.1007/s10495-026-02463-3","DOIUrl":"10.1007/s10495-026-02463-3","url":null,"abstract":"<div><p>Anthracycline-induced cardiotoxicity (AIC), in which ferroptosis-related cardiomyocyte injury has been implicated, remains a major challenge in oncology. This study investigates the therapeutic potential of an apolipoprotein A1 (ApoA1) mimetic peptide, L-4 F, in epirubicin-induced cardiotoxicity (EIC) in a rat model. Rats received epirubicin (2.5 mg/kg/week, i.p.) for six weeks to establish the EIC model, with or without concurrent ApoA1 mimetic treatment (L-4 F, 1 mg/kg/day). Cardiac function was assessed by echocardiography. Myocardial tissues underwent single-nucleus RNA sequencing (snRNA-seq), RegDiffusion-based gene regulatory network inference, Western blot, immunohistochemistry, and ELISA. Mechanistic studies used H9C2 cardiomyoblasts and CMEC-H9C2 Transwell co-culture systems under EPI exposure, with ApoA1 treatment, endothelial IL-33 knockdown, and Ferrostatin-1 (Fer-1) rescue. Glutathione peroxidase 4 (GPX4) expression, intracellular iron, lipid peroxidation, and cell viability were assessed. ApoA1 treatment alleviated diastolic dysfunction and weight loss and partially improved global longitudinal strain. snRNA-seq revealed substantial transcriptional remodeling in cardiomyocytes. RegDiffusion analysis identified coordinated reprogramming of transcription factor regulons, including Ppara, Fos, Egr1, and Klf4. ApoA1 treatment was associated with an anti-ferroptotic pattern of ferroptosis-related gene expression, with relatively higher Gpx4 and Slc7a11 expression and lower Tfrc expression, consistent with increased GPX4 protein levels. Intercellular communication analysis suggested enhanced IL-33/ST2-mediated endothelial-cardiomyocyte signaling following ApoA1 treatment. In vitro, ApoA1 restored GPX4 expression and reduced iron accumulation under EPI stress; these effects were potentiated in co-culture conditions and attenuated by endothelial IL-33 knockdown. In the rescue model, ApoA1 and Fer-1 partially restored viability and reduced MDA. ApoA1 alone did not significantly lower C11-BODIPY oxidation, whereas the combination gave the most consistent effect. ApoA1 attenuates EIC and is associated with modulation of GPX4-linked ferroptosis-related responses. This protective effect may involve endothelial-cardiomyocyte crosstalk, with endothelial IL-33 signaling acting as a partial contributor. These findings highlight a potential cardioprotective mechanism.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 11","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GNMT alleviates heart failure-induced skeletal muscle atrophy by regulating ATP5J2-mediated mitochondrial metabolic reprogramming through succinylation","authors":"Ying Zhao,&nbsp;Ying He,&nbsp;Rui Song,&nbsp;Jimin Chen,&nbsp;Mingxuan Yang,&nbsp;Jinting Liu,&nbsp;Yuan Song,&nbsp;Ying Zhang,&nbsp;Liqing Yao","doi":"10.1007/s10495-026-02404-0","DOIUrl":"10.1007/s10495-026-02404-0","url":null,"abstract":"<div><p>Heart failure (HF) is defined as a condition characterized by abnormalities in the heart's structure or function, which lead to the heart's inability to deliver oxygen to tissues in a timely manner, and it may progress to symptoms such as muscle atrophy of skeletal muscles. Our research primarily focuses on Glycine N-methyltransferase (GNMT), an enzyme that utilizes S-adenosylmethionine (SAM) to catalyze glycine, in order to explore its specific role in HF-induced skeletal muscle atrophy. In this study, an HF rat model induced by abdominal aortic constriction (AAC) and a C2C12 muscle atrophy cell model induced by angiotensin Ⅱ (Ang Ⅱ) were established. Echocardiography, ELISA, and HE staining were used to evaluate the damage of myocardial and gastrocnemius tissues. Immunofluorescence staining was used to assess skeletal muscle atrophy. Western blot, IP, and Co-IP were used to determine the molecular mechanism. In HF rats, the expressions of GNMT and Mitochondrial Fo complex subunit F2 (ATP5J2) were significantly decreased. Overexpression of GNMT/ATP5J2 contributed to alleviate HF-induced skeletal muscle atrophy. GNMT elevated the succinylation level and protein stability of ATP5J2 at lysine 22 (K22) by consuming glycine, and simultaneously reduced its ubiquitination level. Succinylated ATP5J2 improved mitochondrial homeostasis to mitigate HF-induced skeletal muscle atrophy. This study elucidated the function of the GNMT-ATP5J2 axis in HF-induced skeletal muscle atrophy and clarified the underlying molecular mechanism, providing a new theoretical basis for the treatment of HF-induced skeletal muscle atrophy.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 11","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-026-02404-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights and therapeutic implications of mitoxyperilysis: a spatially gated mitochondria-dependent lytic cell death","authors":"Limin Chen,&nbsp;Yimiao Chen,&nbsp;Junfei Zhao,&nbsp;Mengling Xiang,&nbsp;Xianyu Wang,&nbsp;Antao Luo,&nbsp;Adila Abudurexiti,&nbsp;Lei Zhou,&nbsp;Dan Yan,&nbsp;Guijuan Zheng","doi":"10.1007/s10495-026-02462-4","DOIUrl":"10.1007/s10495-026-02462-4","url":null,"abstract":"<div><p>Programmed cell death (PCD) has expanded to more than ten diverse lytic modalities such as pyroptosis, necroptosis, ferroptosis, and disulfidptosis. In 2025, Wang et al. reported in <i>Cell</i> a previously unrecognized form of lytic cell death, termed mitoxyperilysis, in which plasma membrane rupture is driven not by canonical pore-forming or membrane-disrupting enzymatic effectors, but by mitochondria-mediated oxidative injury localized to the cell periphery. This process is initiated by the synergistic combination of innate immune activation and metabolic disruption, referred to as IIAMD, which induces mitochondrial oxidative damage and promotes the sustained retention of injured mitochondria at the plasma membrane, a preceding state termed mitoxyperiosis. Mechanistically, mTORC2, particularly through its defining subunit RICTOR, functions as a central regulatory switch that licenses the transition from tolerated oxidative stress to lethal membrane rupture. By suppressing RhoA-dependent actin remodeling and lamellipodia formation, mTORC2 prevents the spatial clearance of damaged mitochondria from the cell cortex, thereby allowing locally concentrated oxidative stress to overwhelm membrane repair and antioxidant defenses. This two-step framework establishes the concept of spatial licensing in oxidative cell death, emphasizing that lethality depends not only on the amount of reactive oxygen species, but also on their subcellular topology. However, mitoxyperilysis has not yet been implicated in any human disease on the basis of direct evidence. In this review, we summarize the emerging mechanisms of mitoxyperilysis, compare it with established lytic death pathways, and discuss its potential relevance to inflammatory disease, sepsis, ischemic injury, and cancer, as well as therapeutic strategies targeting mTORC2, RhoA signaling, and mitochondrial protection.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 11","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelets as non-canonical immune regulatory nodes: orchestrating T cell dysfunction and immunotherapy resistance in cancer","authors":"Qian Huang,&nbsp;Shuqin Zhang,&nbsp;Ruoshui Liu,&nbsp;Zhijiang Chen,&nbsp;Liming Deng,&nbsp;Jiahong Liao,&nbsp;Yiran Tian,&nbsp;Mi Zou,&nbsp;Jie Peng,&nbsp;Liang Hao","doi":"10.1007/s10495-026-02459-z","DOIUrl":"10.1007/s10495-026-02459-z","url":null,"abstract":"<div><p>Immune checkpoint inhibitors (ICIs) have reshaped cancer treatment; however, durable clinical benefit remains limited by primary and acquired resistance, frequently associated with T cell dysfunction within an immunosuppressive tumor microenvironment. Beyond their classical role in hemostasis, platelets have emerged as active immune modulators capable of shaping antitumor T cell responses. Accumulating evidence indicates that platelets engage T cells through contact-dependent receptor–ligand interactions, immunomodulatory soluble factors, and the transfer of checkpoint-associated extracellular vesicles, thereby reinforcing dysfunctional T cell states and constraining responses to immune checkpoint blockade. In this review, we synthesize current mechanistic insights into platelet–T cell crosstalk, delineate its differential impact across T cell subsets, and integrate these processes into a broader framework of immune evasion and immunotherapy resistance. We further discuss emerging translational strategies aimed at modulating platelet immune functions, including antiplatelet drug repurposing, selective targeting of platelet–immune interfaces, and metabolic interventions to restore T cell fitness. Collectively, this work reframes platelets as non-canonical immune regulatory nodes and highlights platelet–T cell interactions as a therapeutically actionable layer of immune regulation with implications for improving and personalizing cancer immunotherapy.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 11","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149189454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nano-engineered phytochemicals in cancer therapy: mechanistic insights into apoptosis, ferroptosis, tumor microenvironment modulation and drug resistance reversal","authors":"Poonam Sahu,&nbsp;Trilochan Satapathy,&nbsp;Abhisek Satapathy,&nbsp;Abinash Satapathy","doi":"10.1007/s10495-026-02452-6","DOIUrl":"10.1007/s10495-026-02452-6","url":null,"abstract":"<div><p>Cancer progression and therapeutic resistance are driven by interconnected mechanisms involving redox imbalance, metabolic plasticity, epigenetic remodeling and tumor microenvironment (TME)-mediated immune suppression. Conventional “one drug-one target” therapies often fail to overcome these adaptive oncogenic networks, resulting in multidrug resistance and disease relapse. This review aims to explore the therapeutic potential of nano-engineered phytochemicals in cancer management, with emphasis on ferroptosis induction, oncogenic pathway modulation and TME reprogramming for overcoming tumor resistance. A comprehensive narrative review was conducted focusing on recent advances in nano-phytomedicine, ferroptosis-based anticancer strategies and precision nanotherapeutic approaches. Relevant literature was systematically collected from PubMed, Scopus, ScienceDirect and Web of Science databases, considering both preclinical and clinical studies. Retrieved studies were critically analyzed to evaluate the therapeutic effects of nano-engineered phytochemicals on major oncogenic signaling pathways, including PI3K/Akt, NF-κB, STAT3, HIF-1α and NRF2. Mechanistic evidence associated with ferroptosis induction, reactive oxygen species (ROS) modulation, oxidative stress regulation, immune reprogramming and tumor microenvironment (TME) remodeling was systematically assessed. Preclinical studies indicate that nano-engineered phytochemicals can modulate interconnected oncogenic, metabolic, redox and immune pathways and can improve physicochemical and pharmacokinetic properties relative to free phytochemicals. Ferroptosis-associated effects include modulation of glutathione metabolism, GPX4, SLC7A11, iron homeostasis and lipid peroxidation; however, these molecular changes do not independently establish ferroptotic cell death. Evidence for tumour-microenvironment modulation and multidrug-resistance reversal remains predominantly preclinical, whereas human studies are limited and mainly address pharmacokinetic, tolerability or early efficacy outcomes. Nano-engineered phytochemicals represent a promising systems-oriented therapeutic strategy, but their clinical potential remains incompletely established. Future development requires rigorous mechanistic validation, reproducible formulation and manufacturing processes, biomarker-guided clinical evaluation, and comprehensive assessment of biodistribution, toxicity and long-term safety.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div><p><i>Clinical trial</i>: The manuscript is a review article (not a part of Clinical trial), hence no Clinical trial no is applicable.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 11","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149162999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shedding light on the cancer cell death mechanism in photodynamic therapy","authors":"Saeid Moghassemi,&nbsp;Arezoo Dadashzadeh,&nbsp;Olivier Feron,&nbsp;Christiani A. Amorim","doi":"10.1007/s10495-026-02458-0","DOIUrl":"10.1007/s10495-026-02458-0","url":null,"abstract":"<div><p>Photodynamic therapy (PDT) employs the interaction of a photosensitizer, light, and molecular oxygen to generate reactive oxygen species, which induce regulated cell death pathways that contribute to tumor eradication and immune modulation. Despite its clinical utility, the determinants of tumor selectivity remain incompletely understood. Current evidence suggests that PDT selectivity does not arise from a single mechanism but rather from the dynamic interplay among photosensitizer properties, tumor architecture, microenvironmental heterogeneity, and host immune responses. Here, we integrate current mechanistic understanding of PDT-induced cell death and discuss how tumor-specific factors, including enhanced permeability and retention, differential transporter expression, and microenvironmental heterogeneity, modulate photosensitizer accumulation. We further examine how photosensitizer subcellular localization, tumor biology, and immune microenvironment shape therapeutic outcomes. This integrated perspective highlights opportunities to guide the selection and optimization of PDT agents and treatment strategies toward improved selectivity and immunogenicity, while reinforcing PDT as a versatile modality within modern cancer therapy.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 11","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149162974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAF-derived GLG1 drives bladder cancer growth and apoptosis resistance","authors":"Anurima Singh,&nbsp;Parag Jain","doi":"10.1007/s10495-026-02460-6","DOIUrl":"10.1007/s10495-026-02460-6","url":null,"abstract":"","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 11","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149162976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Necroptosis as a key player in cervical cancer progression and management: a systematic review and transcriptomic cross-study consensus analysis","authors":"Seth-Frerich Fobian,&nbsp;Eric Eldering,&nbsp;Jacqueline Tromp,&nbsp;Arlene L. Oei","doi":"10.1007/s10495-026-02440-w","DOIUrl":"10.1007/s10495-026-02440-w","url":null,"abstract":"<div><p>Immunotherapy has improved outcomes for a subset of patients with locally advanced cervical cancer. However, many tumors remain immunologically “cold” and fail to respond. Strategies that enhance tumor immunogenicity are therefore of increasing interest. Necroptosis, a regulated form of inflammatory cell death, has emerged as a potential mechanism capable of promoting the anti-tumor immune responses through the release of damage-associated molecular patterns and enhanced antigen presentation. In this study, we performed a systematic review and transcriptomic cross-study consensus analysis of all studies carried out describing the role and mechanisms of necroptosis occurrence in cervical cancers. We analyzed all published necroptosis-related prognostic gene signatures and integrated these findings into an exploratory transcriptomic analyses to identify mechanistic insights into interlinked biological pathways, and potential therapeutic targets. Following PRISMA guidelines, we analyzed seven published prognostic models, from studies using RNA sequencing and least absolute shrinkage and selection operator (LASSO)-based feature selection to generate a prognostic risk score for patients. We then conducted a comparative analyses of eight overlapping genes and their reported risk score coefficients. Across studies, seven necroptosis-related genes were identified, many of which are functionally linked to mitochondrial transport and permeability regulation, reactive oxygen species (ROS) generation, and inflammatory signaling. Overall, our findings support a key role for necroptosis in cervical cancer, where activation thereof is generally associated with enhanced immune infiltration and activation; thereby improved prognosis. These findings position necroptosis as a promising target for combination therapy strategies aimed at converting immunologically “cold” tumors into more responsive phenotypes. By integrating published signatures with exploratory analyses, we identify potential avenues to modulate necroptotic signaling in ways that may enhance synergy with immunotherapies, and have synthesized a hypothetical cell signaling and interaction diagram. Collectively, this work provides a foundation for future experimental validation and therapeutic development.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 11","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10495-026-02440-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anastasis: an unwelcome guest in cancer therapy","authors":"Yizhi Luo,&nbsp;Yong Lei,&nbsp;Jianmin Deng,&nbsp;Yi Yu,&nbsp;Lu Qian,&nbsp;Yuyan Xiong","doi":"10.1007/s10495-026-02455-3","DOIUrl":"10.1007/s10495-026-02455-3","url":null,"abstract":"<div><p>Anastasis is a newly identified cellular recovery process that enables cells to regain viability after progressing into execution-phase apoptosis. In cancer, this process may allow tumor cells to survive transient cytotoxic stress and subsequently acquire more aggressive phenotypes, including enhanced migration, invasion, and resistance to therapy. Although anastasis has attracted increasing attention, its biological significance and contribution to cancer progression remain incompletely understood. In this review, we summarize the defining features and biological processes of anastasis and critically evaluate current evidence linking post-apoptotic recovery to cancer-associated phenotypes, including apoptosis regulation, metastasis, angiogenesis, oxidative-stress adaptation, and epithelial–mesenchymal transition. We further discuss molecular pathways implicated in anastatic recovery and examine potential therapeutic strategies aimed at limiting post-apoptotic survival in cancer cells. Finally, we highlight major challenges in the field, including the need for more specific biomarkers, physiologically relevant in vivo models, and direct clinical validation, and outline key unresolved questions that should guide future investigation.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 10","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ferroptosis–cuproptosis crosstalk in hematological malignancies: multi-omics insights into gene-regulated cell death and emerging therapeutic opportunities","authors":"Sonakshi Antal,&nbsp;Tushar Anshu,&nbsp;Pawan Kumar Goswami,&nbsp;Dinesh Kumar,&nbsp;Neeraj Choudhary,&nbsp;Anita D. Kadam","doi":"10.1007/s10495-026-02451-7","DOIUrl":"10.1007/s10495-026-02451-7","url":null,"abstract":"<div><p>The broadening field of regulated cell death (RCD) has shown a complex, intertwined web of pathways that are not confined to apoptosis but also to ferroptosis, cuproptosis, necroptosis, and other non-canonical mechanisms, especially in haematological malignancies (HMs). Out of these, ferroptosis and cuproptosis stand out as metabolic-based forms of death that are regulated by iron-dependent and copper-dependent processes, respectively. This review presents the notion of a single ferroptosis-cuproptosis axis, a Metallo-redox network that encompasses lipid peroxidation, mitochondrial dysfunction, and proteotoxic stress to control cell fate decisions. We underscore the fact that haematological cancers use metal ion flux, redox homeostasis, and metabolic plasticity to bypass apoptosis, but are susceptible to other RCD pathways. This work, based on multi-omics methods, such as genomics, transcriptomics, proteomics, metabolomics, and metal omics, describes how integrative modelling can unravel RCD susceptibility landscapes and discover context-specific therapeutic targets. The single-cell and spatial analyses further demonstrate intra-tumoral heterogeneity and switching between death pathways in response to therapeutic pressure. New treatment options that are being developed to address this axis such as ferroptosis inducers, copper ionophores, and complex nanomedicine systems with the ability to deliver therapeutics and modify pathways. The review also covers such challenges of translation as the lack of standardization of biomarkers, clinical trial design, and dynamic stratification of patients. Lastly, suggest an outlook system combining artificial intelligence, synthetic biology, and organoid-based systems to permit precision cell death engineering. Together, this literature makes the ferroptosis-cuproptosis axis a novel change in the outlook of future therapies in haematological cancers.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>The provided diagram illustrates the Ferroptosis-Cuproptosis Axis, showing how iron-driven and copper-driven cell death pathways intersect to influence patient outcomes. By integrating multi-omics data (genomics, transcriptomics, proteomics, and metabolomics) with AI and machine learning, researchers can build predictive models for patient stratification. This computational workflow ultimately helps identify whether a patient will show sensitivity to therapy (leading to cell death) or treatment resistance (leading to tumor survival and disease relapse).</p></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 10","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}