{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:20:09Z","timestamp":1790713209534,"version":"4.1.0"},"reference-count":134,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T00:00:00Z","timestamp":1555459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Clear cell renal cell carcinoma (ccRCC) is the seventh most frequently diagnosed tumor in adults in Europe and represents approximately 2.5% of cancer deaths. The molecular biology underlying renal cell carcinoma (RCC) development and progression has been a key milestone in the management of this type of tumor. The discovery of Von Hippel Lindau (VHL) gene alterations that arouse in 50% of ccRCC patients, leads the identification of an intracellular accumulation of HIF and, consequently an increase of VEGFR expression. This change in cell biology represents a new paradigm in the treatment of metastatic renal cancer by targeting angiogenesis. Currently, there are multiple therapeutic drugs available for advanced disease, including therapies against VEGFR with successful results in patients\u00b4 survival. Other tyrosine kinases\u2019 pathways, including PDGFR, Axl or MET have emerged as key signaling pathways involved in RCC biology. Indeed, promising new drugs targeting those tyrosine kinases have exhibited outstanding efficacy. In this review we aim to present an overview of the central role of these tyrosine kinases\u2019 activities in relevant biological processes for kidney cancer and their usefulness in RCC targeted therapy development. In the immunotherapy era, angiogenesis is still an \u201cold guy\u201d that the medical community is trying to fight using \u201cnew bullets\u201d.<\/jats:p>","DOI":"10.3390\/ijms20081901","type":"journal-article","created":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T07:58:09Z","timestamp":1555487889000},"page":"1901","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Targeting Tyrosine kinases in Renal Cell Carcinoma: \u201cNew Bullets against Old Guys\u201d"],"prefix":"10.3390","volume":"20","author":[{"given":"Teresa","family":"Alonso-Gordoa","sequence":"first","affiliation":[{"name":"Medical Oncology Department, The Ram\u00f3n y Cajal Health Research Institute (IRYCIS), CIBERONC, Alcal\u00e1 University, University Hospital Ramon y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Laura","family":"Garc\u00eda-Bermejo","sequence":"additional","affiliation":[{"name":"Biomarkers and Therapeutic Targets Group and Core Facility, Ram\u00f3n y Cajal Research Institute, (IRYCIS), 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Grande","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, MD Anderson Cancer Center, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Garrido","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, The Ram\u00f3n y Cajal Health Research Institute (IRYCIS), CIBERONC, Alcal\u00e1 University, University Hospital Ramon y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Carrato","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Ram\u00f3n y Cajal Health Research Institute (IRYCIS). CIBERONC, Alcal\u00e1 University, University Hospital Ramon y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4616-0598","authenticated-orcid":false,"given":"Javier","family":"Molina-Cerrillo","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, The Ram\u00f3n y Cajal Health Research Institute (IRYCIS), CIBERONC, Alcal\u00e1 University, University Hospital Ramon y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.ejca.2012.12.027","article-title":"Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012","volume":"49","author":"Ferlay","year":"2013","journal-title":"Eur. J. 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