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Πέμπτη 23 Μαρτίου 2017

FGFR a promising druggable target in cancer: molecular biology and new drugs

Publication date: Available online 23 March 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Rut Porta, Roberto Borea, Andreia Coelho, Shahnavaj Khan, Antonio Araujo, Pablo Reclusa, Tindara Franchina, Nele Van Der Steen, Peter Van Dam, Jose Ferri, Rafael Sirera, Aung Naing, David Hong, Christian Rolfo
IntroductionThe Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR.Areas CoveredThis review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies.Expert opinionMost of the TKR share intracellular signaling pathways; therefore, cancer cells tend to overcome the inhibition of one tyrosine kinase receptor by activating another. The future of TKI (Tyrosine Kinase Inhibitor) therapy will potentially come from multi-targeted TKIs that target different TKR simultaneously.It is crucial to understand the interaction of the FGF-FGFR axis with other known driver TKRs. Based on this,it is possible to develop therapeutic strategies targeting multiple connected TKRs at once. One correct step in this direction is the reassessment of multi target inhibitors considering the FGFR status of the tumor. Another opportunity arises from assessing the use of FGFR TKI on patients harboring FGFR alterations.



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