Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors involved in many biological processes. Deregulated FGFR signaling plays an important role in tumor development and progression in different cancer types. FGFR genomic alterations, including FGFR gene fusions that originate by chromosomal rearrangements, represent a promising therapeutic target. Next-generation-sequencing (NGS) approaches have significantly improved the discovery of FGFR gene fusions and their detection in clinical samples. A variety of FGFR inhibitors have been developed, and several studies are trying to evaluate the efficacy of these agents in molecularly selected patients carrying FGFR genomic alterations. In this review, we describe the most frequent FGFR aberrations in human cancer. We also discuss the different approaches employed for the detection of FGFR fusions and the potential role of these genomic alterations as prognostic/predictive biomarkers.
Small cell lung cancer is an aggressive disease for which few therapeutic options are currently available. Although patients initially respond to therapy, they rapidly relapse. Up to today, no biomarkers for guiding treatment of SCLC patients have been identified. SCLC patients rarely undergo surgery and often the available tissue samples are inadequate for biomarker analysis. Circulating tumor cells (CTCs) are rare cells in the peripheral blood that might be used as surrogates of tissue samples. Different methodological approaches have been developed for studies of CTCs in SCLC. In addition to CTC count, which might provide prognostic and predictive information, genomic and transcriptomic analyses allow the characterization of molecular profiles of CTCs and permit the study of tumor heterogeneity. The employment of CTC-derived xenografts offers complementary information to genomic analyses and CTC enumeration about the mechanisms involved in the sensitivity/resistance to treatments. Using these approaches, CTC analysis is providing relevant information on SCLC biology that might aid in the development of personalized therapeutic strategies for SCLC patients.