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

• Published in: Critical reviews in oncology/hematology 2017-05, Vol.113, p.256-267
• Main Authors: Porta, Rut, Borea, Roberto, Coelho, Andreia, Khan, Shahnavaj, Araujo, Antonio, Reclusa, Pablo, Franchina, Tindara, Van Der Steen, Nele, Van Dam, Peter, Ferri, Jose, Sirera, Rafael, Naing, Aung, Hong, David, Rolfo, Christian
• Format: Article
• Language: English
• Subjects: Cancer; Drug Resistance, Neoplasm; FGF; FGFR; FGFR inhibitors; Fibroblast Growth Factors - antagonists & inhibitors; Fibroblast Growth Factors - physiology; Gene Fusion; Hematology, Oncology and Palliative Medicine; Humans; Molecular Targeted Therapy; Mutation; Neoplasms - drug therapy; Neoplasms - genetics; Protein Kinase Inhibitors - therapeutic use; Receptors, Fibroblast Growth Factor - antagonists & inhibitors; Receptors, Fibroblast Growth Factor - genetics; Receptors, Fibroblast Growth Factor - physiology; Signal Transduction - physiology
• ISSN: 1040-8428; 1879-0461
• DOI: 10.1016/j.critrevonc.2017.02.018

Abstract Introduction The 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 Covered This 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 opinion Most 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.