{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:19:07Z","timestamp":1792801147962,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":88,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Natural Science Foundation of China","award":["(Grant No. 82505141)."],"award-info":[{"award-number":["(Grant No. 82505141)."]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The Hunan Science Fund for Distinguished Young Scholars","award":["2025JJ20098"],"award-info":[{"award-number":["2025JJ20098"]}]},{"name":"High-level Talent Research Initiation Fund Project of Hunan University of Chinese Medicine","award":["0004010, 0003003002"],"award-info":[{"award-number":["0004010, 0003003002"]}],"id":[{"id":"https:\/\/ror.org\/01tsmvz08","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Exp Clin Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Clear cell renal cell carcinoma (ccRCC) is characterized by extensive lipid metabolic reprogramming that drives tumor progression and therapeutic resistance. Although sterol regulatory element-binding protein 1 (SREBP1) is a central regulator of lipogenesis in ccRCC, the upstream mechanisms governing its activation remain poorly defined. Here, we investigated the role of FAM120A in SREBP1-dependent lipid metabolism and evaluated the therapeutic potential of the natural product Soulangianolide A (SA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Stable knockdown of SREBP1 or FAM120A was established in ccRCC cells to assess lipid metabolism and malignant phenotypes. The antitumor activity and molecular mechanism of SA were investigated using integrated lipidomic, transcriptomic, proteomic, biochemical, and xenograft analyses, together with molecular docking, pull-down assays, surface plasmon resonance, and cellular thermal shift assays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genetic depletion of SREBP1 suppressed lipogenic gene expression, intracellular lipid accumulation, and malignant phenotypes in ccRCC cells. FAM120A promoted SREBP1 nuclear accumulation and transcriptional activity, whereas SA inhibited SREBP1 signaling, reduced lipid storage, and induced apoptosis. Multi-omics analyses revealed extensive metabolic remodeling characterized by depletion of triglycerides and membrane lipids, accompanied by accumulation of ceramides and acylcarnitines, indicative of a lipotoxic state. Mechanistically, SA directly bound FAM120A at Cys531, disrupted the FAM120A-SREBP1 complex, impaired SREBP1 nuclear activity, and consequently attenuated lipid-dependent PPAR\u03b3 signaling. In xenograft models, SA significantly suppressed tumor growth, reduced intratumoral lipid accumulation, inhibited SREBP1-driven lipogenic signaling, and potentiated the antitumor efficacy of MK-6482.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings identify the FAM120A-SREBP1-PPAR\u03b3 axis as a critical driver of lipid metabolic reprogramming in ccRCC, establish FAM120A as a direct molecular target of SA, and demonstrate that pharmacological disruption of this pathway effectively suppresses tumor growth. These findings provide a mechanistic rationale for targeting lipid metabolic reprogramming in ccRCC and support SA as a promising metabolism-targeted therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13046-026-03788-2","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T13:15:53Z","timestamp":1784294153000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Soulangianolide A targets FAM120A to disrupt SREBP1-driven lipid metabolic reprogramming and suppress clear cell renal cell carcinoma"],"prefix":"10.1186","volume":"45","author":[{"given":"Wei","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zishu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangshuai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaofang","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanglin","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohe","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"3788_CR1","doi-asserted-by":"publisher","first-page":"17009","DOI":"10.1038\/nrdp.2017.9","volume":"3","author":"J J Hsieh","year":"2017","unstructured":"Hsieh J J, Purdue M P, Signoretti S, et al. Renal cell carcinoma [J]. Nat Rev Dis Primers. 2017;3:17009.","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"3788_CR2","first-page":"7","volume":"71","author":"R L Siegel","year":"2021","unstructured":"Siegel R L, Miller K D, Fuchs H E, et al. Cancer Statistics, 2021 [J]. CA Cancer J Clin. 2021;71(1):7\u201333.","journal-title":"CA Cancer J Clin"},{"issue":"5","key":"3788_CR3","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1016\/j.eururo.2018.01.005","volume":"73","author":"B C Leibovich","year":"2018","unstructured":"Leibovich B C, Lohse C M, Cheville JC, et al. Predicting Oncologic Outcomes in Renal Cell Carcinoma After Surgery [J]. Eur Urol. 2018;73(5):772\u201380.","journal-title":"Eur Urol"},{"issue":"6","key":"3788_CR4","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/nrurol.2011.64","volume":"8","author":"V A Valera","year":"2011","unstructured":"Valera V A, Merino MJ. Misdiagnosis of clear cell renal cell carcinoma [J]. Nat Rev Urol. 2011;8(6):321\u201333.","journal-title":"Nat Rev Urol"},{"issue":"12","key":"3788_CR5","doi-asserted-by":"publisher","first-page":"3106","DOI":"10.1158\/2159-8290.CD-21-0211","volume":"11","author":"R Riscal","year":"2021","unstructured":"Riscal R, Bull C J, Mesaros C, et al. Cholesterol Auxotrophy as a Targetable Vulnerability in Clear Cell Renal Cell Carcinoma [J]. Cancer Discov. 2021;11(12):3106\u201325.","journal-title":"Cancer Discov"},{"issue":"7","key":"3788_CR6","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/nrneph.2017.59","volume":"13","author":"H I Wettersten","year":"2017","unstructured":"Wettersten H I, Aboud O A, Lara P N JR, et al. Metabolic reprogramming in clear cell renal cell carcinoma [J]. Nat Rev Nephrol. 2017;13(7):410\u20139.","journal-title":"Nat Rev Nephrol"},{"issue":"1","key":"3788_CR7","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/s41420-025-02479-9","volume":"11","author":"Y Zhang","year":"2025","unstructured":"Zhang Y, Zhang S, Sun H, et al. The pathogenesis and therapeutic implications of metabolic reprogramming in renal cell carcinoma [J]. Cell Death Discov. 2025;11(1):186.","journal-title":"Cell Death Discov"},{"issue":"3","key":"3788_CR8","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/s41588-024-01662-5","volume":"56","author":"J Hu","year":"2024","unstructured":"Hu J, Wang S G, Hou Y, et al. Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression [J]. Nat Genet. 2024;56(3):442\u201357.","journal-title":"Nat Genet"},{"issue":"2","key":"3788_CR9","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.euo.2024.09.002","volume":"8","author":"L Marandino","year":"2025","unstructured":"Marandino L, Campi R, Amparore D, et al. Neoadjuvant and Adjuvant Immune-based Approach for Renal Cell Carcinoma: Pros, Cons, and Future Directions [J]. Eur Urol Oncol. 2025;8(2):494\u2013509.","journal-title":"Eur Urol Oncol"},{"issue":"6","key":"3788_CR10","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/j.eururo.2025.02.020","volume":"87","author":"A Bex","year":"2025","unstructured":"Bex A, Ghanem Y A, Albiges L, et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2025 Update [J]. Eur Urol. 2025;87(6):683\u201396.","journal-title":"Eur Urol"},{"issue":"4","key":"3788_CR11","doi-asserted-by":"publisher","first-page":"100987","DOI":"10.1016\/j.gendis.2023.04.022","volume":"11","author":"Y HE","year":"2024","unstructured":"He Y, Qi S, Chen L. The roles and mechanisms of SREBP1 in cancer development and drug response [J]. Genes Dis. 2024;11(4):100987.","journal-title":"Genes Dis"},{"issue":"8","key":"3788_CR12","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1002\/cac2.70038","volume":"45","author":"M Lao","year":"2025","unstructured":"Lao M, Zhang X, Li Z, et al. Lipid metabolism reprograming by SREBP1-PCSK9 targeting sensitizes pancreatic cancer to immunochemotherapy [J]. Cancer Commun (Lond). 2025;45(8):1010\u201337.","journal-title":"Cancer Commun (Lond)"},{"key":"3788_CR13","doi-asserted-by":"publisher","first-page":"155360","DOI":"10.1016\/j.phymed.2024.155360","volume":"128","author":"M Chen","year":"2024","unstructured":"Chen M, Li H, Zheng S, et al. Nobiletin targets SREBP1\/ACLY to induce autophagy-dependent cell death of gastric cancer cells through PI3K\/Akt\/mTOR signaling pathway [J]. Phytomedicine. 2024;128:155360.","journal-title":"Phytomedicine"},{"issue":"22","key":"3788_CR14","doi-asserted-by":"publisher","first-page":"2578","DOI":"10.1101\/gad.1854309","volume":"23","author":"T F Osborne","year":"2009","unstructured":"Osborne T F, Espenshade P J. Evolutionary conservation and adaptation in the mechanism that regulates SREBP action: what a long, strange tRIP it\u2019s been [J]. Genes Dev. 2009;23(22):2578\u201391.","journal-title":"Genes Dev"},{"issue":"9","key":"3788_CR15","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1172\/JCI0215593","volume":"109","author":"JD Horton","year":"2002","unstructured":"Horton J D, Goldstein J L, Brown M S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver [J]. J Clin Invest. 2002;109(9):1125\u201331.","journal-title":"J Clin Invest"},{"issue":"15","key":"3788_CR16","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.2174\/13816128113199990486","volume":"20","author":"D Guo","year":"2014","unstructured":"Guo D, Bell E H, Mischel P, et al. Targeting SREBP-1-driven lipid metabolism to treat cancer [J]. Curr Pharm Des. 2014;20(15):2619\u201326.","journal-title":"Curr Pharm Des"},{"issue":"16","key":"3788_CR17","doi-asserted-by":"publisher","first-page":"3010","DOI":"10.1016\/j.molcel.2023.07.017","volume":"83","author":"S Cho","year":"2023","unstructured":"Cho S, Chun Y, He L, et al. FAM120A couples SREBP-dependent transcription and splicing of lipogenesis enzymes downstream of mTORC1 [J]. Mol Cell. 2023;83(16):3010\u2013e268.","journal-title":"Mol Cell"},{"issue":"1","key":"3788_CR18","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s42003-024-06097-6","volume":"7","author":"L Niu","year":"2024","unstructured":"Niu L, Li Y, Huang G, et al. FAM120A deficiency improves resistance to cisplatin in gastric cancer by promoting ferroptosis [J]. Commun Biol. 2024;7(1):399.","journal-title":"Commun Biol"},{"issue":"9","key":"3788_CR19","first-page":"2273","volume":"48","author":"W L Shi","year":"2023","unstructured":"Shi W L, Wang J, Ma Y, et al. [Advances in research methods for biosynthetic pathway analysis of active ingredients in traditional Chinese medicine] [J]. Zhongguo Zhong Yao Za Zhi. 2023;48(9):2273\u201383.","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"3788_CR20","doi-asserted-by":"crossref","unstructured":"Naeem A, Hu P, Yang M, et al. Natural Products as Anticancer Agents: Current Status and Future Perspectives [J]. Molecules. 2022;27(23):8367.","DOI":"10.3390\/molecules27238367"},{"key":"3788_CR21","doi-asserted-by":"publisher","first-page":"1659831","DOI":"10.3389\/fphar.2025.1659831","volume":"16","author":"J Chen","year":"2025","unstructured":"Chen J, Zhao Z, Lin L, et al. Aucklandia lappa Decne: a review of its botany, cultivation, ethnopharmacology, phytochemistry, pharmacology, and practical applications [J]. Front Pharmacol. 2025;16:1659831.","journal-title":"Front Pharmacol"},{"key":"3788_CR22","doi-asserted-by":"publisher","first-page":"111550","DOI":"10.1016\/j.intimp.2024.111550","volume":"128","author":"W Luo","year":"2024","unstructured":"Luo W, Song Z, Xu G, et al. LicochalconeB inhibits cGAS-STING signaling pathway and prevents autoimmunity diseases [J]. Int Immunopharmacol. 2024;128:111550.","journal-title":"Int Immunopharmacol"},{"key":"3788_CR23","doi-asserted-by":"publisher","first-page":"624112","DOI":"10.3389\/fendo.2021.624112","volume":"12","author":"M Hernandez-Quiles","year":"2021","unstructured":"Hernandez-Quiles M, Broekema M F, Kalkhoven E. PPARgamma in Metabolism, Immunity, and Cancer: Unified and Diverse Mechanisms of Action [J]. Front Endocrinol (Lausanne). 2021;12:624112.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"3788_CR24","doi-asserted-by":"publisher","first-page":"108391","DOI":"10.1016\/j.pharmthera.2023.108391","volume":"245","author":"H Chen","year":"2023","unstructured":"Chen H, Tan H, Wan J, et al. PPAR-\u03b3 signaling in nonalcoholic fatty liver disease: Pathogenesis and therapeutic targets [J]. Pharmacol Ther. 2023;245:108391.","journal-title":"Pharmacol Ther"},{"issue":"1","key":"3788_CR25","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s13679-025-00612-4","volume":"14","author":"D Kounatidis","year":"2025","unstructured":"Kounatidis D, Vallianou N G, Rebelos E, et al. The Many Facets of PPAR-\u03b3 Agonism in Obesity and Associated Comorbidities: Benefits, Risks, Challenges, and Future Directions [J]. Curr Obes Rep. 2025;14(1):19.","journal-title":"Curr Obes Rep"},{"issue":"22","key":"3788_CR26","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1056\/NEJMoa2103425","volume":"385","author":"E Jonasch","year":"2021","unstructured":"Jonasch E, Donskov F, Iliopoulos O, et al. Belzutifan for Renal Cell Carcinoma in von Hippel-Lindau Disease [J]. N Engl J Med. 2021;385(22):2036\u201346.","journal-title":"N Engl J Med"},{"issue":"2","key":"3788_CR27","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1007\/s11912-022-01354-5","volume":"25","author":"W W Choi","year":"2023","unstructured":"Choi W W, Boland J L, Kalola A, et al. Belzutifan (MK-6482): Biology and Clinical Development in Solid Tumors [J]. Curr Oncol Rep. 2023;25(2):123\u20139.","journal-title":"Curr Oncol Rep"},{"issue":"8","key":"3788_CR28","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1056\/NEJMoa2313906","volume":"391","author":"T K Choueiri","year":"2024","unstructured":"Choueiri T K, Powles T, Peltola K, et al. Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma [J]. N Engl J Med. 2024;391(8):710\u201321.","journal-title":"N Engl J Med"},{"issue":"11","key":"3788_CR29","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1038\/s41585-024-00876-w","volume":"21","author":"C Liao","year":"2024","unstructured":"Liao C, Hu L, Zhang Q. Von Hippel-Lindau protein signalling in clear cell renal cell carcinoma [J]. Nat Rev Urol. 2024;21(11):662\u201375.","journal-title":"Nat Rev Urol"},{"issue":"1","key":"3788_CR30","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1038\/s41420-024-01944-1","volume":"10","author":"X Hua","year":"2024","unstructured":"Hua X, Ge S, Zhang L, et al. MED15 is upregulated by HIF-2\u03b1 and promotes proliferation and metastasis in clear cell renal cell carcinoma via activation of SREBP-dependent fatty acid synthesis [J]. Cell Death Discov. 2024;10(1):188.","journal-title":"Cell Death Discov"},{"issue":"7","key":"3788_CR31","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/nrneph.2017.59","volume":"13","author":"H I Wettersten","year":"2017","unstructured":"Wettersten H I, Aboud O A, Lara P N, et al. Metabolic reprogramming in clear cell renal cell carcinoma [J]. Nat Rev Nephrol. 2017;13(7):410\u20139.","journal-title":"Nat Rev Nephrol"},{"issue":"1","key":"3788_CR32","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.ccell.2015.12.004","volume":"29","author":"A A Hakimi","year":"2016","unstructured":"Hakimi A A, Reznik E, Lee C H, et al. An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma [J]. Cancer Cell. 2016;29(1):104\u201316.","journal-title":"Cancer Cell"},{"key":"3788_CR33","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.canlet.2021.05.012","volume":"514","author":"D Shen","year":"2021","unstructured":"Shen D, Gao Y, Huang Q, et al. E2F1 promotes proliferation and metastasis of clear cell renal cell carcinoma via activation of SREBP1-dependent fatty acid biosynthesis [J]. Cancer Lett. 2021;514:48\u201362.","journal-title":"Cancer Lett"},{"issue":"12","key":"3788_CR34","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1158\/0008-5472.CAN-14-3650","volume":"75","author":"R A Bartolom\u00e9","year":"2015","unstructured":"Bartolom\u00e9 R A, Garc\u00eda-Palmero I, Torres S, et al. IL13 Receptor \u03b12 Signaling Requires a Scaffold Protein, FAM120A, to Activate the FAK and PI3K Pathways in Colon Cancer Metastasis [J]. Cancer Res. 2015;75(12):2434\u201344.","journal-title":"Cancer Res"},{"key":"3788_CR35","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1146\/annurev-physiol-031620-093815","volume":"83","author":"B Chaurasia","year":"2021","unstructured":"Chaurasia B, Summers S A. Ceramides in Metabolism: Key Lipotoxic Players [J]. Annu Rev Physiol. 2021;83:303\u201330.","journal-title":"Annu Rev Physiol"},{"key":"3788_CR36","doi-asserted-by":"publisher","first-page":"101936","DOI":"10.1016\/j.molmet.2024.101936","volume":"83","author":"N Wajapeyee","year":"2024","unstructured":"Wajapeyee N, Beamon T C, Gupta R. Roles and therapeutic targeting of ceramide metabolism in cancer [J]. Mol Metab. 2024;83:101936.","journal-title":"Mol Metab"},{"issue":"1","key":"3788_CR37","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s43018-023-00702-z","volume":"5","author":"F C E Vogel","year":"2024","unstructured":"Vogel F C E, Chaves-Filho A B, Schulze A. Lipids as mediators of cancer progression and metastasis [J]. Nat Cancer. 2024;5(1):16\u201329.","journal-title":"Nat Cancer"},{"issue":"1","key":"3788_CR38","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/s41389-022-00420-8","volume":"11","author":"S Vasseur","year":"2022","unstructured":"Vasseur S, Guillaumond F. Lipids in cancer: a global view of the contribution of lipid pathways to metastatic formation and treatment resistance [J]. Oncogenesis. 2022;11(1):46.","journal-title":"Oncogenesis"},{"issue":"12","key":"3788_CR39","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1038\/s41569-021-00569-6","volume":"18","author":"D Montaigne","year":"2021","unstructured":"Montaigne D, Butruille L, Staels B. PPAR control of metabolism and cardiovascular functions [J]. Nat Rev Cardiol. 2021;18(12):809\u201323.","journal-title":"Nat Rev Cardiol"},{"key":"3788_CR40","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.molmet.2018.05.013","volume":"14","author":"D J Sanchez","year":"2018","unstructured":"Sanchez D J, Steger D J, Skuli N, et al. PPAR\u03b3 is dispensable for clear cell renal cell carcinoma progression [J]. Mol Metab. 2018;14:139\u201349.","journal-title":"Mol Metab"},{"key":"3788_CR41","doi-asserted-by":"publisher","first-page":"643065","DOI":"10.3389\/fonc.2021.643065","volume":"11","author":"F Petitprez","year":"2021","unstructured":"Petitprez F, Ayadi M, De Reyni\u00e8s A, et al. Review of Prognostic Expression Markers for Clear Cell Renal Cell Carcinoma [J]. Front Oncol. 2021;11:643065.","journal-title":"Front Oncol"},{"issue":"9","key":"3788_CR42","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1056\/NEJMoa2026982","volume":"384","author":"T K Choueiri","year":"2021","unstructured":"Choueiri T K, Powles T, Burotto M, et al. Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma [J]. N Engl J Med. 2021;384(9):829\u201341.","journal-title":"N Engl J Med"},{"issue":"1","key":"3788_CR43","doi-asserted-by":"publisher","first-page":"530","DOI":"10.4081\/oncol.2021.530","volume":"15","author":"S Gkolfinopoulos","year":"2021","unstructured":"Gkolfinopoulos S, Psyrri A, Bamias A. Clear-cell renal cell carcinoma - A comprehensive review of agents used in the contemporary management of advanced\/metastatic disease [J]. Oncol Rev. 2021;15(1):530.","journal-title":"Oncol Rev"}],"container-title":["Journal of Experimental &amp; Clinical Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13046-026-03788-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-026-03788-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13046-026-03788-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T16:06:26Z","timestamp":1791907586000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13046-026-03788-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3788"],"URL":"https:\/\/doi.org\/10.1186\/s13046-026-03788-2","relation":{},"ISSN":["1756-9966"],"issn-type":[{"value":"1756-9966","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]},"assertion":[{"value":"24 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors have read and agreed to the published version of the manuscript.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"215"}}