Apoptosis最新文献

{"title":"Exploring regulated cell death in renal cell carcinoma: mechanistic insights and therapeutic perspectives","authors":"Guanyu Zhu,&nbsp;Hangbiao Zhang,&nbsp;Yuanan Li,&nbsp;Wenjie Ma,&nbsp;Yuntao Yao,&nbsp;Donghao Lyu,&nbsp;Bingnan Lu,&nbsp;Yuanbo Zong,&nbsp;Keqin Dong,&nbsp;Wang Zhou,&nbsp;Yifan Liu,&nbsp;Xingang Cui,&nbsp;Xiuwu Pan","doi":"10.1007/s10495-026-02425-9","DOIUrl":"10.1007/s10495-026-02425-9","url":null,"abstract":"<div><p>Renal cell carcinoma (RCC) is the third most prevalent urological malignancy, characterized by histological heterogeneity and complex molecular landscapes. Although established regimens, including surgical intervention, targeted therapies and immunotherapy, effectively manage early-stage disease, patients with advanced RCC still have a poor prognosis. The expanding spectrum of regulated cell death (RCD), ranging from established apoptosis and ferroptosis to emerging modalities like cuproptosis, disulfidptosis and ammonia-induced cell death, offers novel mechanistic insights into tumor vulnerabilities. This tumor progression and subsequent therapeutic resistance are substantially mediated by dysregulated networks of RCD. To systematically deconstruct this mechanistic complexity, this review stratifies RCD into three specific functional dimensions: precise protein signaling, intracellular homeostasis dysregulation, and physiological dysfunction. Because RCC intrinsically evades cascade-governed pathways such as apoptosis to survive immune elimination, its inherent metabolic reprogramming concomitantly creates paradoxical vulnerabilities. Consequently, these tumors exhibit profound susceptibility to homeostasis-disrupting modalities like ferroptosis, cuproptosis, disulfidptosis, and ammonia-induced cell death. Extending this mechanistic framework beyond clear cell RCC (ccRCC), we define the unique metabolic and redox dependencies of underrepresented non-clear cell variants, including papillary RCC (pRCC), chromophobe RCC (chRCC), fumarate hydratase (FH)-deficient RCC and TFE3-rearranged RCC. By evaluating current RCD-targeted pharmacological interventions, this review highlights critical opportunities to exploit these functional dependencies, offering rational approaches to overcome intrinsic resistance and complement existing therapies. Ultimately, integrating this multidimensional RCD framework with multi-omics profiling facilitates a deeper biological understanding of renal tumors and provides a necessary foundation to accelerate the development of precision oncology.</p></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":"149103235","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":"Ru3: a novel ruthenium-based compound overcomes cisplatin resistance in non-small cell lung cancer via the E2F2-IGFBP3-GPX4 pathway","authors":"Yiting Lu,&nbsp;Shiming Wu,&nbsp;Ying Jiang,&nbsp;Meishu Wang,&nbsp;Xinyu Liao,&nbsp;Jian Zhang,&nbsp;Junqi Xiang,&nbsp;Hua Yang,&nbsp;Min Yu,&nbsp;Jiang Min,&nbsp;Chen Fu,&nbsp;Yunlong Lei","doi":"10.1007/s10495-026-02447-3","DOIUrl":"10.1007/s10495-026-02447-3","url":null,"abstract":"<div><p>Cisplatin resistance remains a major hurdle in non-small cell lung cancer (NSCLC) treatment. Here, we designed and synthesized a novel ruthenium-based compound, which selectively kills cisplatin-resistant NSCLC cells while sparing parental cells. Mechanistically, Ru3 triggers mitochondrial damage and reactive oxygen species (ROS) accumulation. In addition, it upregulates the transcription factor E2F2, which directly represses IGFBP3 expression. IGFBP3 normally scavenges ROS via the GPX4 system; thus, E2F2-mediated IGFBP3 suppression disrupts this antioxidant defense, exacerbating ROS levels and cell death. Notably, cisplatin-resistant cells exhibit elevated GPX4 and IGFBP3 expression, making them particularly vulnerable to Ru3. This study elucidates the E2F2-IGFBP3-GPX4 axis as a novel therapeutic vulnerability and highlights Ru3 as a promising agent for refractory NSCLC.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div><p>Ru3's Mechanism of Action on Cisplatin Resistant Lung Cancer Cells</p><ol>\u0000 <li>\u0000 <span>1.</span>\u0000 \u0000 <p>Ru3 induces mitochondrial damage, which promotes the accumulation of ROS and ultimately triggers cell death.</p>\u0000 \u0000 </li>\u0000 <li>\u0000 <span>2.</span>\u0000 \u0000 <p>Ru3 upregulates E2F2, enabling it to directly bind to the IGFBP3 promoter and suppress IGFBP3 expression, which inhibits GPX4 expression and further exacerbating lethal ROS accumulation .</p>\u0000 \u0000 </li>\u0000 <li>\u0000 <span>3.</span>\u0000 \u0000 <p>Treatment with Ru3 resulted in significant cell death in cisplatin-resistant lung cancer cells, yet had a minimal impact on parental lung cancer cells, which attributed to the suppression of the TRX antioxidant system in cisplatin-resistant cells, coupled with an increase in the activity of the GSH antioxidant system.</p>\u0000 \u0000 </li>\u0000 </ol></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/PMC13633971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103243","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":"The role of lysosome-dependent cell death in cancer","authors":"Jia-Feng Li,&nbsp;Ke Zhang,&nbsp;Xiao-Han Zhang,&nbsp;Xue-Chun Qu,&nbsp;Jing Zhang,&nbsp;Pei-Hao Sun,&nbsp;Ruo-Yu Xu,&nbsp;Wei-Rong Si,&nbsp;Qi-Ying Jiang,&nbsp;Dong-Dong Wu","doi":"10.1007/s10495-026-02442-8","DOIUrl":"10.1007/s10495-026-02442-8","url":null,"abstract":"<div><p>Lysosome-dependent cell death (LDCD) is a distinct mode of regulated cell death, which differs from canonical cell death pathways such as apoptosis and necrosis. Its key features include lysosomal membrane permeabilization and the downstream signaling cascades triggered by cathepsin release. Recent studies have demonstrated that LDCD exerts dual, intricate influences on cancer initiation, progression, immune homeostasis and therapeutic responses. It not only confers a survival advantage upon cancer cells but also represents a promising target for targeted antitumor therapy. This review systematically summarizes the molecular mechanisms underlying LDCD, its dual regulatory roles in cancer, and LDCD-based anticancer therapeutic strategies, and outlines future research directions. Ultimately, this work sheds light on the mechanistic link between LDCD and oncogenesis, providing a rationale for the development of targeted antitumor strategies.</p></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":"149103274","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":"Metabolic vulnerabilities in multiple myeloma: targeting iron and amino acid metabolism to induce ferroptosis","authors":"Qi Li,&nbsp;Weimin Zhang,&nbsp;Guangcan Gao,&nbsp;Yilei Shi,&nbsp;Ruijing Hu,&nbsp;Xinyuan Zhang,&nbsp;Chuan He,&nbsp;Han Zhang,&nbsp;Wenzhuo Zhuang,&nbsp;Bingzong Li","doi":"10.1007/s10495-026-02449-1","DOIUrl":"10.1007/s10495-026-02449-1","url":null,"abstract":"<div><p>Could ferroptosis, a novel cell death pathway, offer a potential therapeutic strategy for multiple myeloma (MM)? Our previous research showed that ferroptosis is suppressed in MM patients, with varying sensitivities among MM cells. In this study, metabolomic analysis highlighted the pivotal role of amino acid metabolism, rather than lipid metabolism, in determining MM cells’ sensitivity to ferroptosis. We further analyzed iron metabolism, another key factor influencing ferroptosis sensitivity, by collecting peripheral blood samples from 120 MM patients. Our analysis revealed a significant reduction in the levels of transferrin (TF), an essential iron-transporting protein. Moreover, low TF levels were associated with significantly worse progression-free survival and overall survival. Erastin treatment together with TF supplementation markedly enhanced ferroptosis in MM cells in vitro and in xenograft models. MM cells suppressed TF secretion by monocytes in the bone marrow microenvironment, contributing to the decreased TF levels in MM patients. The transcription factor CEBPB, found in MM cell-derived extracellular vesicles, plays a key role in this process. In conclusion, Our findings identify amino acid metabolism and iron metabolism as distinct metabolic features associated with ferroptosis sensitivity in MM. Ferroptosis, induced by erastin and TF, holds promise as a potential therapeutic strategy for MM and provides new insights for developing more effective therapies.</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":"149103303","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 role of vitamin D signalling in β cell apoptosis: a systematic review","authors":"Donglai Li,&nbsp;Nick Norris,&nbsp;Yousun An,&nbsp;Jenny E. Gunton","doi":"10.1007/s10495-026-02453-5","DOIUrl":"10.1007/s10495-026-02453-5","url":null,"abstract":"<div><h3>Background</h3><p>Vitamin D signalling, primarily through the vitamin D receptor (VDR), regulates cellular survival and programmed cell death. This systematic review aims to synthesise current evidence on the role of vitamin D in pancreatic β-cell apoptosis.</p><h3>Methods</h3><p>Medline, Embase, and Scopus were searched for original studies investigating vitamin D, vitamin D analogues, or VDR-related interventions in experimental models of β-cell apoptosis or programmed cell death.</p><h3>Results</h3><p>26 studies were included. Across in vitro, ex vivo, and in vivo models, vitamin D signalling protected β-cells against apoptosis induced by cytokine-mediated inflammation, oxidative stress, glucotoxicity, lipotoxicity, streptozotocin exposure, and diabetic stress. These effects were associated with reduced NF-κB signalling, nitric oxide and reactive oxygen species production, improved mitochondrial stability, modulation of Bcl-2 family proteins, inhibition of endoplasmic reticulum stress, and regulation of pyroptosis, ferroptosis, and autophagy-related survival mechanisms. VDR activation also supported β-cell identity, insulin secretion, and β-cell mass preservation. In contrast, calcitriol-associated growth inhibition and increased apoptosis were reported in βTC insulinoma models.</p><h3>Conclusion</h3><p>Vitamin D signalling generally appears cytoprotective in β-cells exposed to inflammatory, oxidative, and metabolic stress. However, its effects on β-cell survival are model- and context-dependent, reflecting differences in cellular background, experimental stressors, and methods used to assess cell death.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 10","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103254","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":"HPRT1 drives mitochondrial metabolic reprogramming and immunosuppressive microenvironment in oral squamous cell carcinoma","authors":"Qilin Hu,&nbsp;Wenhan Liu,&nbsp;Xiangyu Chen,&nbsp;Shuyi Wang,&nbsp;Lutong Cai,&nbsp;Ruotong Liu,&nbsp;Tuan Wang,&nbsp;Zhaoqi Wu,&nbsp;Li Li,&nbsp;Lei Xue","doi":"10.1007/s10495-026-02454-4","DOIUrl":"10.1007/s10495-026-02454-4","url":null,"abstract":"<div><p>Mitochondrial metabolic reprogramming is a hallmark of tumor progression, yet its gene-level determinants in oral squamous cell carcinoma (OSCC) remain poorly defined. Here, we integrated multi-omics analyses, machine learning, and experimental validation to elucidate the mitochondrial energy metabolism landscape in OSCC. A six-gene prognostic signature (<i>CTSG, HPRT1, SLC20A1, TRIB3, MTFP1, and ADA</i>) was constructed using Cox regression, CoxBoost, and random survival forest algorithms, which accurately predicted patient survival and delineated distinct immune microenvironment patterns in OSCC. Among these genes, <i>HPRT1</i> emerged as a pivotal mitochondrial metabolic driver. Single-cell transcriptomics revealed that <i>HPRT1</i> was predominantly expressed in malignant epithelial clusters and correlated with proliferative and immunosuppressive phenotypes. Validation in patient tissues and xenograft models confirmed that <i>HPRT1</i> overexpression promoted tumor growth. Multiplex immunofluorescence on tissue microarrays demonstrated that high <i>HPRT1</i> expression was associated with increased M2 macrophage infiltration and reduced densities of CD8⁺ T cells and M1 macrophages, indicating its role in establishing an immunosuppressive tumor microenvironment. Structure-based virtual screening, molecular dynamics simulations, and in vivo xenograft experiments identified troxerutin as a potential <i>HPRT1</i>-binding compound with favorable binding stability and free energy. Collectively, our study identifies <i>HPRT1</i> as a key regulator linking mitochondrial metabolism and immune evasion in OSCC, providing a promising therapeutic target and supporting drug repurposing strategies for precision oncology.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 10","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035003","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 cGAS-STING pathway: mechanistic basis, dual biological functions and translational therapeutic advances","authors":"Minjue Shan,&nbsp;Yan Liao,&nbsp;Ziyou Lin,&nbsp;Lizhou Song,&nbsp;Wangzheqi Zhang,&nbsp;Ruoyu Jiang,&nbsp;Haoling Zhang,&nbsp;Yadong Guo,&nbsp;Fei Su","doi":"10.1007/s10495-026-02450-8","DOIUrl":"10.1007/s10495-026-02450-8","url":null,"abstract":"<div><p>The cGAS-STING pathway acts as a central and highly potent innate immune sensing system in the human body. It can efficiently recognize cytoplasmic double-stranded DNA originating from invading exogenous pathogens and damaged endogenous host cells. This unique molecular recognition feature lays a solid foundation for its multiple vital physiological functions, including host defense against infections, tumor immune surveillance, and the maintenance of normal cellular homeostasis. This review systematically investigates the distinct functional states and biological behaviors of the cGAS-STING pathway under a variety of disease conditions. When the pathway is activated properly at the right time and with appropriate intensity, it can effectively eliminate invasive pathogens and exert potent anti-tumor effects to restrain malignant progression. On the contrary, aberrant, excessive or long-term persistent activation of this signaling cascade will trigger severe inflammatory reactions, which further drive the onset and deterioration of autoimmune disorders, neurodegenerative diseases and multiple aging-related illnesses. Moreover, this article also summarizes the latest research progress of targeted agonists and inhibitors developed for this pathway. We elaborate on their application scenarios, core advantages and existing bottlenecks, aiming to provide comprehensive theoretical references and research directions for follow-up basic mechanistic studies and clinical transformation of cGAS-STING targeted therapeutic strategies.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 10","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035004","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":"DONSON links tumor-cell survival to MIF-associated macrophage remodeling in small cell lung cancer","authors":"Qingwu Du,&nbsp;Rui Li,&nbsp;Ting Mei,&nbsp;Shuxiang Ma,&nbsp;Yufeng Wu,&nbsp;Peng Li,&nbsp;Lili Wang,&nbsp;Zhen He,&nbsp;Qiming Wang","doi":"10.1007/s10495-026-02441-9","DOIUrl":"10.1007/s10495-026-02441-9","url":null,"abstract":"<div><p>Small-cell lung cancer (SCLC) responds poorly to immune checkpoint blockade, but how tumor-cell states shape the myeloid microenvironment remains unclear. Here we identify downstream neighbor of SON (DONSON) as a prognostic factor associated with macrophage-related programmes in SCLC. Across bulk transcriptomic cohorts, clinical specimens, and mouse and human single-cell atlases, DONSON is preferentially expressed in malignant epithelial cells and is associated with neuroendocrine features and an immunosuppressive phenotype. Genetic perturbation of <i>DONSON</i> alters SCLC-cell proliferation, apoptosis and tumor growth, as well as macrophage migration and M2-like polarization. DONSON abundance also tracks with p38 MAPK activity and macrophage migration inhibitory factor (MIF) expression and secretion. Pharmacological inhibition, constitutively active MKK6 rescue, and MIF gain- and loss-of-function experiments support functional contributions of p38 and MIF to these phenotypes. Regorafenib alters the thermal stability of endogenous DONSON and enhances anti-PD-1 activity in syngeneic SCLC models, accompanied by increased proportions of CD86-positive macrophages and IFN-γ-positive CD8⁺ T cells. These findings implicate a DONSON-associated p38-MIF programme in neuroendocrine SCLC and tumor-macrophage crosstalk, nominating this pathway for further therapeutic investigation.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 10","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035162","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":"Targeting LAMP2 synergizes with gemcitabine to inhibit bladder cancer progression via modulating STING degradation and regulating macrophage phenotypes","authors":"Yue Lv,&nbsp;Qiang Yin,&nbsp;Wuheng Li,&nbsp;Leihong Deng,&nbsp;Jiasheng Liu,&nbsp;Haolong Lv,&nbsp;Peng Zhang,&nbsp;Yihang Qiu,&nbsp;Difeng Guo,&nbsp;Rui Tao,&nbsp;Xiuguo Gan,&nbsp;Fanghua Xu,&nbsp;Zan Liu,&nbsp;Yongquan Wang","doi":"10.1007/s10495-026-02446-4","DOIUrl":"10.1007/s10495-026-02446-4","url":null,"abstract":"<div><p>Bladder cancer (BLCA) is an aggressive malignancy characterized by metastasis and drug resistance, creating an urgent demand for novel therapeutic targets. The lysosomal protein LAMP2 acts as a key oncogenic driver in BLCA and modulates the degradation of STING. As reported in prior studies, mechanistically, p62-mediated macroautophagy and HSC70-dependent chaperone-mediated autophagy (CMA) facilitate STING degradation. LAMP2 increases STING ubiquitination, leading to its lysosomal degradation in BLCA. Moreover, LAMP2 knockdown suppresses BLCA cell proliferation and migration. In our experimental systems, it also induces M1-type tumor-associated macrophages (TAMs) polarization and reduces TAM infiltration. RNF5 and TRIM56 are known to mediate K48/K63-linked ubiquitination of STING. Here, we demonstrate LAMP2 modulates this ubiquitination pattern in BLCA. Via virtual screening, we discover MRGPRX4 modulator-2 (Mm-2), a LAMP2-binding small molecule with anti-tumor activity against BLCA. Combined with gemcitabine (GEM), Mm-2 blocks autophagic flux and activates STING signaling. It also alters TAM phenotypes in our in vitro and in vivo models. The LAMP2-STING-TAMs axis shows potential as a therapeutic target for modulating the tumor immune microenvironment (TME) and affecting drug response in BLCA.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>As a core lysosomal protein, LAMP2 is indispensable for autophagy and cellular waste clearance. LAMP2 knockdown impairs p62-related macroautophagy and HSC70-dependent CMA. It is well known that these autophagic pathways regulate STING and its downstream signaling pathways. Additionally, LAMP2 can interfere with the proteasomal degradation of STING by regulating the expression of RNF5 and TRIM56. In our experimental models, LAMP2 inhibition induces mild M1 polarization and reduces infiltration of TAMs. LAMP2 knockdown upregulates IFN-β, which activates macrophage IFNAR1 and triggers the JAK1/STAT1 pathway within our cell and animal models. This study clarifies the intrinsic role of LAMP2 in BLCA progression. Furthermore, we identified Mm-2 as a candidate LAMP2-targeting agent acting on STING signaling via drug screening and molecular docking. Mm-2 acts synergistically with GEM in preclinical models, offering basic research references for LAMP2-related therapeutic exploration.</p></div></div></figure></div></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 10","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029692","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 emerging roles of disulfidptosis in cancer","authors":"Yong-Hao Zhu,&nbsp;Yi-Xuan Liu,&nbsp;Yu-Xiang Liu,&nbsp;Cun-Yuan Yu,&nbsp;Xin-Yu Li,&nbsp;Wen-Cang Zhao,&nbsp;Zi-Han Zhu,&nbsp;Hao-Xuan Liu,&nbsp;Bo Wang,&nbsp;Ke Zhang,&nbsp;Dong-Dong Wu","doi":"10.1007/s10495-026-02444-6","DOIUrl":"10.1007/s10495-026-02444-6","url":null,"abstract":"<div><p>Cancer persists as a significant global health burden, with conventional therapeutic approaches frequently constrained by drug resistance and disease relapse, underscoring the urgent requirement for innovative treatment modalities. Recent advances in regulated cell death have uncovered promising therapeutic avenues for cancer. Amidst these newly identified processes, disulfidptosis—a distinct type of programmed cell death triggered by disulfide stress—has garnered significant attention because of its specific metabolic reliance. The underlying mechanism centers on pathological intracellular cystine accumulation coupled with depletion of NADPH reducing equivalents, stemming from elevated levels of the cystine transporter SLC7A11 during metabolic stress states such as glucose deprivation. This cascade induces aberrant disulfide bonding followed by actin cytoskeleton disruption, ultimately resulting in cellular demise. Evidence suggests that disulfidptosis-related genes exhibit altered expression across various malignancies, including lung, liver, and colorectal cancers, and are strongly correlated with disease progression and patient outcomes. Prognostic models constructed based on bioinformatics not only demonstrate good predictive efficacy but also reflect characteristics of the tumor immune microenvironment. This process reveals a fundamental weakness in cancer cells after metabolic reprogramming, establishing the induction of disulfidptosis via SLC7A11 inhibition or modulation of associated metabolic pathways as a promising new anticancer approach. It also provides a rationale for combination strategies with chemotherapy, targeted therapy, and immunotherapy. Nonetheless, its interaction with different cell death mechanisms (including ferroptosis), the variability observed across various cancer types, and the translation to clinical applications remain significant challenges and key avenues for future investigation.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"31 10","pages":""},"PeriodicalIF":9.0,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029713","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}