{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:42:19Z","timestamp":1790937739310,"version":"4.1.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2012,7,17]],"date-time":"2012-07-17T00:00:00Z","timestamp":1342483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100008272","name":"Novartis Pharmaceuticals Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Non-clear cell renal cell carcinomas (nccRCCs) comprise a heterogenous and poorly characterized group of tumor types for which few treatments have been approved. Although targeted therapies have become the cornerstones of systemic treatment for metastatic renal cell carcinoma, patients with nccRCC have been excluded from many pivotal clinical trials. As such, robust clinical evidence supporting the use of these agents in patients with nccRCC is lacking. Here, we review the disparate nccRCC subtypes, the criteria for diagnosis, and the prognoses associated with each subtype, in addition to evaluating the potential use of mammalian target of rapamycin (mTOR) inhibitors in treating patients with nccRCC. Both genetic analyses and preclinical research indicate a central role for mTOR in nccRCC; a therapy that targets this ubiquitous regulator of cellular signaling could prove efficacious across various tumor subtypes. Results from recent studies exploring targeted therapies as both monotherapy and combination therapy have provided early indications of efficacy in patients with nccRCC. Exploratory analyses support further research with the mTOR inhibitors everolimus and temsirolimus in patients with nccRCC. Current clinical practice guidelines support the use of mTOR inhibitors in patients with nccRCC; however, these recommendations are based on low levels of evidence. Further results from randomized, controlled clinical trials are needed to determine the optimal choice of therapy for patients with nccRCC. Results from ongoing clinical trials of mTOR inhibitors and other agents in nccRCC, as well as their impact on the nccRCC treatment paradigm, are eagerly awaited.<\/jats:p>","DOI":"10.1634\/theoncologist.2012-0038","type":"journal-article","created":{"date-parts":[[2012,7,18]],"date-time":"2012-07-18T22:22:26Z","timestamp":1342650146000},"page":"1051-1062","source":"Crossref","is-referenced-by-count":16,"title":["Non-Clear Cell Renal Cell Carcinoma: Does the Mammalian Target of Rapamycin Represent a Rational Therapeutic Target?"],"prefix":"10.1093","volume":"17","author":[{"given":"Laurence","family":"Albiges","sequence":"first","affiliation":[{"name":"a Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Molinie","sequence":"additional","affiliation":[{"name":"b Department of Pathology, H\u00f4pital Saint Joseph, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Escudier","sequence":"additional","affiliation":[{"name":"a Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,7,17]]},"reference":[{"key":"2021122308223492000_B1","volume-title":"SEER stat fact sheets: Kidney and renal pelvis","author":"National Cancer Institute"},{"key":"2021122308223492000_B2","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1016\/j.ejca.2009.12.014","article-title":"Estimates of cancer incidence and mortality in Europe in 2008","volume":"46","author":"Ferlay","year":"2010","journal-title":"Eur J Cancer"},{"key":"2021122308223492000_B3","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1056\/NEJMra043172","article-title":"Renal-cell carcinoma","volume":"353","author":"Cohen","year":"2005","journal-title":"N Engl J 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inhibitor therapy","volume":"48","author":"Grunwald","year":"2012","journal-title":"Eur J Cancer"},{"issue":"suppl 1","key":"2021122308223492000_B41","article-title":"Safety and efficacy of everolimus in patients with non-clear cell renal cell carcinoma refractory to VEGF-targeted therapy: A subgroup analysis of the REACT expanded-access program","volume":"47","author":"Blank","year":"2011","journal-title":"Eur J Cancer"},{"key":"2021122308223492000_B42","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1200\/JCO.2007.13.3223","article-title":"Efficacy of sunitinib and sorafenib in metastatic papillary and chromophobe renal cell carcinoma","volume":"26","author":"Choueiri","year":"2008","journal-title":"J Clin Oncol"},{"key":"2021122308223492000_B43","doi-asserted-by":"crossref","first-page":"5788","DOI":"10.1200\/JCO.2008.18.8821","article-title":"Phase II study of erlotinib in patients with locally advanced or metastatic papillary histology renal cell cancer: SWOG 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