{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:38:52Z","timestamp":1787020732039,"version":"build-2736575974"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":38,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LTGY24H160020"],"award-info":[{"award-number":["LTGY24H160020"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82503414"],"award-info":[{"award-number":["82503414"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2023KY931"],"award-info":[{"award-number":["2023KY931"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"DOI":"10.1186\/s12964-026-02783-6","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T07:22:49Z","timestamp":1774336969000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Disulfidptosis induced by intermittent fasting and metformin enhances the efficacy of anti-PD-1 therapy in renal cancer"],"prefix":"10.1186","volume":"24","author":[{"given":"Hongru","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjiao","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhinan","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinchen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zitong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"2783_CR1","unstructured":"Clear cell renal cell carcinoma. ontogeny and mechanisms of lethality - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/33144689\/. Cited 12 May 2025."},{"key":"2783_CR2","unstructured":"Single-cell deconvolution of a specific malignant cell population as a poor prognostic biomarker in low-risk clear cell renal cell carcinoma patients - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/36801089\/.\u00a0Cited 13 May 2025."},{"issue":"11","key":"2783_CR3","doi-asserted-by":"publisher","first-page":"2888","DOI":"10.1158\/0008-5472.CAN-21-0628","volume":"81","author":"RM Chabanon","year":"2021","unstructured":"Chabanon RM, Morel D, Eychenne T, Colmet-Daage L, Bajrami I, Dorvault N, et al. PBRM1 Deficiency confers synthetic lethality to DNA repair inhibitors in cancer. Cancer Res. 2021;81(11):2888\u2013902.","journal-title":"Cancer Res"},{"issue":"2","key":"2783_CR4","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.eururo.2023.04.003","volume":"84","author":"BH Cotta","year":"2023","unstructured":"Cotta BH, Choueiri TK, Cieslik M, Ghatalia P, Mehra R, Morgan TM, et al. Current landscape of genomic biomarkers in clear cell renal cell carcinoma. Eur Urol. 2023;84(2):166\u201375.","journal-title":"Eur Urol"},{"key":"2783_CR5","unstructured":"A pan-cancer analysis of PBAF complex mutations and their association with immunotherapy response - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/32820162\/.\u00a0Cited 12 May 2025."},{"key":"2783_CR6","unstructured":"Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/38350680\/.\u00a0Cited 12 May 2025."},{"key":"2783_CR7","unstructured":"Kidney cancer: Diabetes and low serum cholesterol are risk factors for RCC - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/24980192\/. Cited 12 May 2025."},{"issue":"3","key":"2783_CR8","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/nrendo.2013.256","volume":"10","author":"I Pernicova","year":"2014","unstructured":"Pernicova I, Korbonits M. Metformin\u2013mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol. 2014;10(3):143\u201356.","journal-title":"Nat Rev Endocrinol"},{"issue":"14","key":"2783_CR9","doi-asserted-by":"publisher","first-page":"2358","DOI":"10.1158\/0008-5472.CAN-22-3042","volume":"83","author":"X Huang","year":"2023","unstructured":"Huang X, Sun T, Wang J, Hong X, Chen H, Yan T, et al. Metformin reprograms tryptophan metabolism to stimulate CD8\u2009+\u2009T-cell function in colorectal cancer. Cancer Res. 2023;83(14):2358\u201371.","journal-title":"Cancer Res"},{"issue":"5","key":"2783_CR10","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1016\/j.ccell.2019.03.007","volume":"35","author":"M Elgendy","year":"2019","unstructured":"Elgendy M, Cir\u00f2 M, Hosseini A, Weiszmann J, Mazzarella L, Ferrari E, et al. Combination of hypoglycemia and metformin impairs tumor metabolic plasticity and growth by modulating the PP2A-GSK3\u03b2-MCL-1 Axis. Cancer Cell. 2019;35(5):798\u2013e8155.","journal-title":"Cancer Cell"},{"issue":"5","key":"2783_CR11","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.tem.2016.02.006","volume":"27","author":"RK Sayyid","year":"2016","unstructured":"Sayyid RK, Fleshner NE. Diabetes mellitus type 2: a driving force for urological complications. Trends Endocrinol Metab TEM. 2016;27(5):249\u201361.","journal-title":"Trends Endocrinol Metab TEM"},{"issue":"3","key":"2783_CR12","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/s41556-023-01091-2","volume":"25","author":"X Liu","year":"2023","unstructured":"Liu X, Nie L, Zhang Y, Yan Y, Wang C, Colic M, et al. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. Nat Cell Biol. 2023;25(3):404\u201314.","journal-title":"Nat Cell Biol"},{"key":"2783_CR13","unstructured":"Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/38697165\/. Cited 12 May 2025."},{"key":"2783_CR14","unstructured":"Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/37069149\/. Cited 12 May 2025."},{"key":"2783_CR15","unstructured":"VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/38618956\/. Cited 12 May 2025."},{"issue":"8","key":"2783_CR16","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1158\/2159-8290.CD-17-0292","volume":"7","author":"YF Gu","year":"2017","unstructured":"Gu YF, Cohn S, Christie A, McKenzie T, Wolff N, Do QN, et al. Modeling renal cell carcinoma in mice: Bap1 and Pbrm1 inactivation drive tumor grade. Cancer Discov. 2017;7(8):900\u201317.","journal-title":"Cancer Discov"},{"issue":"12","key":"2783_CR17","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1016\/j.celrep.2017.02.074","volume":"18","author":"AM Nargund","year":"2017","unstructured":"Nargund AM, Pham CG, Dong Y, Wang PI, Osmangeyoglu HU, Xie Y, et al. The SWI\/SNF protein PBRM1 restrains VHL-loss-driven clear cell renal cell carcinoma. Cell Rep. 2017;18(12):2893\u2013906.","journal-title":"Cell Rep"},{"key":"2783_CR18","unstructured":"MYC activation cooperates with Vhl and Ink4a\/Arf loss to induce clear cell renal cell carcinoma - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/28593993\/. Cited 13 May 2025."},{"issue":"2","key":"2783_CR19","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s41585-022-00659-1","volume":"20","author":"J Walton","year":"2023","unstructured":"Walton J, Lawson K, Prinos P, Finelli A, Arrowsmith C, Ailles L. PBRM1, SETD2 and BAP1 - the trinity of 3p in clear cell renal cell carcinoma. Nat Rev Urol. 2023;20(2):96\u2013115.","journal-title":"Nat Rev Urol"},{"key":"2783_CR20","unstructured":"Expression and Mutation patterns of PBRM1, BAP1 and SETD2 mirror specific evolutionary subtypes in clear cell renal cell carcinoma - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/30660076\/.\u00a0Cited 13 May 2025."},{"issue":"6","key":"2783_CR21","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1158\/0008-5472.CAN-07-5276","volume":"68","author":"W Xia","year":"2008","unstructured":"Xia W, Nagase S, Montia AG, Kalachikov SM, Keniry M, Su T, et al. BAF180 is a critical regulator of p21 induction and a tumor suppressor mutated in breast cancer. Cancer Res. 2008;68(6):1667\u201374.","journal-title":"Cancer Res"},{"key":"2783_CR22","doi-asserted-by":"publisher","first-page":"e37925","DOI":"10.7554\/eLife.37925","volume":"7","author":"L Liao","year":"2018","unstructured":"Liao L, Liu ZZ, Langbein L, Cai W, Cho EA, Na J, et al. Multiple tumor suppressors regulate a HIF-dependent negative feedback loop via ISGF3 in human clear cell renal cancer. eLife. 2018;7:e37925.","journal-title":"eLife"},{"issue":"1","key":"2783_CR23","doi-asserted-by":"publisher","first-page":"2026","DOI":"10.1038\/s41467-017-02245-1","volume":"8","author":"J Espana-Agusti","year":"2017","unstructured":"Espana-Agusti J, Warren A, Chew SK, Adams DJ, Matakidou A. Loss of PBRM1 rescues VHL dependent replication stress to promote renal carcinogenesis. Nat Commun. 2017;8(1):2026.","journal-title":"Nat Commun"},{"issue":"3","key":"2783_CR24","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/s40265-020-01461-2","volume":"81","author":"CL Braal","year":"2021","unstructured":"Braal CL, Jongbloed EM, Wilting SM, Mathijssen RHJ, Koolen SLW, Jager A. Inhibiting CDK4\/6 in Breast Cancer with Palbociclib, Ribociclib, and Abemaciclib: Similarities and Differences. Drugs. 2021;81(3):317\u201331.","journal-title":"Drugs"},{"issue":"6","key":"2783_CR25","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1002\/med.21354","volume":"35","author":"L Vym\u011btalov\u00e1","year":"2015","unstructured":"Vym\u011btalov\u00e1 L, Kry\u0161tof V. Potential clinical uses of CDK inhibitors: lessons from synthetic lethality screens. Med Res Rev. 2015;35(6):1156\u201374.","journal-title":"Med Res Rev"},{"issue":"6","key":"2783_CR26","doi-asserted-by":"publisher","first-page":"2885","DOI":"10.1158\/0008-5472.CAN-05-4412","volume":"66","author":"S Pattingre","year":"2006","unstructured":"Pattingre S, Levine B. Bcl-2 inhibition of autophagy: a new route to cancer? Cancer Res. 2006;66(6):2885\u20138.","journal-title":"Cancer Res"},{"key":"2783_CR27","unstructured":"PARP inhibitors: synthetic lethality in the clinic - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/28302823\/ Cited 13 May 2025."},{"key":"2783_CR28","unstructured":"Targeting DNA repair in cancer: beyond PARP Inhibitors - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/28003236\/. Cited 13 May 2025."},{"key":"2783_CR29","unstructured":"A guide to cell death pathways - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/38110635\/. Cited 13 May 2025."},{"issue":"2","key":"2783_CR30","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.cell.2023.11.044","volume":"187","author":"K Newton","year":"2024","unstructured":"Newton K, Strasser A, Kayagaki N, Dixit VM. Cell death. Cell. 2024;187(2):235\u201356.","journal-title":"Cell"},{"issue":"Suppl0","key":"2783_CR31","doi-asserted-by":"publisher","first-page":"S78","DOI":"10.1016\/j.semcancer.2015.03.001","volume":"35","author":"RM Mohammad","year":"2015","unstructured":"Mohammad RM, Muqbil I, Lowe L, Yedjou C, Hsu HY, Lin LT, et al. Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol. 2015;35(Suppl0):S78\u2013103.","journal-title":"Semin Cancer Biol"},{"key":"2783_CR32","unstructured":"Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/35725836\/. Cited 13 May 2025."},{"key":"2783_CR33","doi-asserted-by":"publisher","first-page":"105299","DOI":"10.1016\/j.phrs.2020.105299","volume":"163","author":"Y Zhou","year":"2021","unstructured":"Zhou Y, Liu L, Tao S, Yao Y, Wang Y, Wei Q, et al. Parthanatos and its associated components: promising therapeutic targets for cancer. Pharmacol Res. 2021;163:105299.","journal-title":"Pharmacol Res"},{"key":"2783_CR34","unstructured":"ATP6V0D1 promotes alkaliptosis by blocking STAT3-mediated lysosomal pH homeostasis - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/36640329\/. Cited 13 May 2025."},{"key":"2783_CR35","unstructured":"GPR1 and CMKLR1 control lipid metabolism to support the development of clear cell renal cell carcinoma - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/38640229\/. Cited 13 May 2025."},{"key":"2783_CR36","doi-asserted-by":"publisher","first-page":"8840590","DOI":"10.1155\/2021\/8840590","volume":"2021","author":"KJ Wang","year":"2021","unstructured":"Wang KJ, Meng XY, Chen JF, Wang KY, Zhou C, Yu R, et al. Emodin induced necroptosis and inhibited glycolysis in the renal cancer cells by enhancing ROS. Oxid Med Cell Longev. 2021;2021:8840590.","journal-title":"Oxid Med Cell Longev"},{"key":"2783_CR37","unstructured":"Methuosis inducer SGI-1027 cooperates with everolimus to promote apoptosis and pyroptosis by triggering lysosomal membrane permeability in renal cancer - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/39119834\/. Cited 13 May 2025."},{"key":"2783_CR38","unstructured":"Hypoxia-triggered ERR\u03b1 acetylation enhanced its oncogenic role and promoted progression of renal cell carcinoma by coordinating autophagosome-lysosome fusion - PubMed. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/39820331\/. Cited 13 May 2025."},{"issue":"3","key":"2783_CR39","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41419-023-05719-x","volume":"14","author":"L Kang","year":"2023","unstructured":"Kang L, Wang D, Shen T, Liu X, Dai B, Zhou D, et al. PDIA4 confers resistance to ferroptosis via induction of ATF4\/SLC7A11 in renal cell carcinoma. Cell Death Dis. 2023;14(3):193.","journal-title":"Cell Death Dis"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-026-02783-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-026-02783-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-026-02783-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T01:53:06Z","timestamp":1777600386000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12964-026-02783-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2783"],"URL":"https:\/\/doi.org\/10.1186\/s12964-026-02783-6","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]},"assertion":[{"value":"3 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All human tissue research in this study obtained approval from the Urology department of Zhejiang University Affiliated Forth Hospital(K2024182) and performed in accordance with the Declaration of Helsinki. All participants provided informed consent. Animal experiments procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Zhejiang University Center for Animal Experiment (ZJU20241020).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"261"}}