title: Targeting FGFR Signaling in Cancer.
abstract: The fibroblast growth factor signaling pathway (FGFR signaling) is an evolutionary conserved signaling cascade that regulates several basic biologic processes, including tissue development, angiogenesis, and tissue regeneration. Substantial evidence indicates that aberrant FGFR signaling is involved in the pathogenesis of cancer. Recent developments of deep sequencing technologies have allowed the discovery of frequent molecular alterations in components of FGFR signaling among several solid tumor types. Moreover, compelling preclinical models have demonstrated the oncogenic potential of these aberrations in driving tumor growth, promoting angiogenesis, and conferring resistance mechanisms to anticancer therapies. Recently, the field of FGFR targeting has exponentially progressed thanks to the development of novel agents inhibiting FGFs or FGFRs, which had manageable safety profiles in early-phase trials. Promising treatment efficacy has been observed in different types of malignancies, particularly in tumors harboring aberrant FGFR signaling, thus offering novel therapeutic opportunities in the era of precision medicine. The most exciting challenges now focus on selecting patients who are most likely to benefit from these agents, increasing the efficacy of therapies with the development of novel potent compounds and combination strategies, and overcoming toxicities associated with FGFR inhibitors. After examination of the basic and translational research studies that validated the oncogenic potential of aberrant FGFR signaling, this review focuses on recent data from clinical trials evaluating FGFR targeting therapies and discusses the challenges and perspectives for the development of these agents.
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Villejuif, France. University Paris Sud, INSERM U981, Predictive Biomarkers and New Therapeutic Strategies in Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Touat
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
authors.forename: Ecaterina
authors.initials: E
authors.lastname: Ileana
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Villejuif, France. University Paris Sud, INSERM U981, Predictive Biomarkers and New Therapeutic Strategies in Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Postel-Vinay
authors.affiliation: University Paris Sud, INSERM U981, Predictive Biomarkers and New Therapeutic Strategies in Oncology, Gustave Roussy, Villejuif, France. Department of Medical Oncology, Gustave Roussy, Villejuif, France. fandre@igr.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.affiliation: Drug Development Department (DITEP), Gustave Roussy, Villejuif, France. University Paris Sud, INSERM U981, Predictive Biomarkers and New Therapeutic Strategies in Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D017468:Receptors, Fibroblast Growth Factor