{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:46:19Z","timestamp":1782279979875,"version":"3.54.5"},"reference-count":101,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Clear cell renal cell carcinoma is the most common histological subtype of kidney cancer, and its development is often related to mutations in the VHL gene. Inactivation of the VHL gene leads to accumulation of HIF-2\u03b1. The accumulation of HIF-2\u03b1 activates multiple signaling pathways, promoting tumor growth and proliferation. The treatment strategies for clear cell renal cell carcinoma mainly include surgical resection, targeted drugs, and immune checkpoint inhibitors. Previous targeted treatments have mostly been tyrosine kinase inhibitors. In recent years, the HIF-2\u03b1 inhibitor Belzutifan has been approved by the FDA for the treatment of clear cell renal cell carcinoma due to its specificity in blocking the HIF-2\u03b1 signaling pathway and its ability to inhibit tumor growth. This article, based on HIF-2\u03b1, provides an overview of the pathogenesis, diagnosis, and treatment of clear cell renal cell carcinoma, with a focus on the clinical trial results of Belzutifan, offering direction and information for the clinical treatment of clear cell renal cell carcinoma.<\/jats:p>","DOI":"10.3389\/fmed.2026.1822724","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:47:05Z","timestamp":1782276425000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Overview of clear cell renal cell carcinoma: from mechanisms to clinical"],"prefix":"10.3389","volume":"13","author":[{"given":"Han","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Jilin Province People's Hospital","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingda","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, The First Hospital of Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingming","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, The First Hospital of Jilin University","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, China-Japan Union Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.3322\/caac.21494","article-title":"Cancer statistics for Hispanics\/Latinos, 2018","volume":"68","author":"Miller","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.ccell.2015.12.004","article-title":"An integrated metabolic atlas of clear cell renal cell carcinoma","volume":"29","author":"Hakimi","year":"2016","journal-title":"Cancer 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