This review is an overview on the ongoing trials

This review is an overview on the ongoing trials involving anti-FGF-FGFR therapies (Wu et al., 2013).
Pathway
FGFR in cancer A recent study comparing more than 4800 tumor tissue samples has shown that 7.1% of all tumor types have genetic alterations in the FGF-FGFR axis. The aberrations percentages were analyzed for the different FGFRs subfamilies, showing that the most frequent alterations affects FGFR1 (49%) followed by FGFR3 (23%) and FGFR2 (19%), with FGFR4 being the least affected (7%). Furthermore, a small range of patients presented with multiple aberrations (5%). The FGFR family alterations are more common in women than in men (17.6% vs 10.0%). This data is of great scientific value because it shows that an alteration of this pathway is the third most present after TP53 and KRAS anomalies (Harding and Nechiporuk, 2012, Helsten et al., 2015).
Therapeutics opportunities against FGFR
Conclusions
Expert opinion
Conflicts of interest
Introduction Advances in sequencing technology have enabled comprehensive genomic analyses of NSCLC, including squamous cell carcinoma (SCC), adenocarcinoma, and sarcomatoid carcinoma. Although NSCLC was previously thought of as a relatively homogenous disease, we now understand that it comprises subsets of diseases driven by distinct molecular changes. Targeted agents against alterations in EGFR, ROS1, ALK receptor tyrosine kinase gene (ALK), and BRAF have resulted in impressive therapeutic responses and have become the standard frontline therapy for patients whose cancers harbor these mutations.4, 5, 6, 7, 8 The salubrinal growth factor receptor (FGFR) is a family of four receptor tyrosine kinases (fibroblast growth factor receptor 1 gene [FGFR1], fibroblast growth factor receptor 2 gene [FGFR2], fibroblast growth factor receptor 3 gene [FGFR3], and fibroblast growth factor receptor 4 gene [FGFR4]) that when bound to their ligands, lead to the downstream activation of diverse pathways, including phospholipase Cγ, mitogen-activated protein kinase, AKT, and signal transducer and activator of transcription. FGFRs play a key role in various cellular functions associated with proliferation and survival. Alterations in FGFR have been reported in a multitude of solid malignancies, including lung, breast, urothelial, melanoma, cholangiocarcinoma, and prostate cancers. These alterations lead to dysregulation and include gain-of-function mutations, amplification, and formation of aberrant fusion proteins that allow for ligand-independent signaling. The incidence of alterations in FGFR, especially amplification of FGFR1, has been reported to be higher in SCC of the lung than in adenocarcinoma (22% versus 3%). FGFR1 amplifications are also seen more commonly in current smokers; in contrast, most targetable mutations have been found in patients with lung adenocarcinoma who are never-smokers or light former smokers. Multikinase inhibitors with anti-FGFR activity, as well as specific pan-FGFR inhibitors, are in various stages of clinical development, and their efficacy is being evaluated in clinical trials.12, 13 FGFR fusions are of particular interest, as preclinical work and emerging clinical data suggest that they convey sensitivity to FGFR inhibition.14, 15, 16 In solid tumors, FGFR is frequently the 5' fusion partner, with the breakpoint found most frequently in introns or exons 17, 18, or 19, resulting in intact extracellular, transmembrane, and kinase domains. The maintenance of the kinase domain has been shown to be critical to the function of the fusion protein. Almost all FGFR fusion partners contain a dimerization domain that allows for autophosphorylation and activation of FGFR signaling. One of the most common fusion proteins is FGFR3–transforming acidic coiled-coil containing 3 (TACC3). Transforming acidic coiled-coil containing 3 gene (TACC3) encodes for a C-terminal coiled-coil domain. The fusion occurs by a tandem duplication event and results in activation of FGFR3 signaling. The FGFR3-TACC3 fusion was first described in glioblastoma multiforme, but has subsequently been detected in various tumor types. In NSCLC, however, although FGFR1 amplification has been defined in several data sets, diverse FGFR fusions have not been well described.