Targeting Tyrosine kinases in Renal Cell Carcinoma: "New Bullets against Old Guys"

• Published in: International journal of molecular sciences Vol. 20; no. 8; p. 1901
• Main Authors: Alonso-Gordoa, Teresa, García-Bermejo, María Laura, Grande, Enrique, Garrido, Pilar, Carrato, Alfredo, Molina-Cerrillo, Javier
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17-04-2019; MDPI
• Subjects: Accumulation; Angiogenesis; Axl; Axl protein; Cancer therapies; Cell adhesion & migration; Chromosome 3; Chromosomes; Cytokines; Disease; Drug development; Drugs; Epigenetics; Fibroblast Growth factor Receptor (FGFR); Genes; Kidney cancer; Kinases; Ligands; Medical diagnosis; Medical prognosis; Metastases; Metastasis; Mortality; Mutation; Platelet Derived Growth Factor Receptor (PDGFR); Projectiles; Renal cell carcinoma; Review; Survival; Tumor suppressor genes; Tumors; Tyrosine; Tyrosine kinase; Tyrosine-Protein Kinase Met (MET); Vascular endothelial growth factor; Vascular endothelial growth factor receptor (VEGFR); VHL protein; Tyrosine kinase; Axl; Kidney cancer; Tyrosine-Protein Kinase Met (MET); Platelet Derived Growth Factor Receptor (PDGFR); Vascular endothelial growth factor receptor (VEGFR); Fibroblast Growth factor Receptor (FGFR)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20081901

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 (
) 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´ survival. Other tyrosine kinases' 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' activities in relevant biological processes for kidney cancer and their usefulness in RCC targeted therapy development. In the immunotherapy era, angiogenesis is still an "old guy" that the medical community is trying to fight using "new bullets".