Fibroblast Growth Factor (FGF) Receptor/FGF Inhibitors: Novel Targets and Strategies for Optimization of Response of Solid Tumors

Cinta Hierro; Jordi Rodon; Josep Tabernero

doi:10.1053/j.seminoncol.2015.09.027

Fibroblast Growth Factor (FGF) Receptor/FGF Inhibitors: Novel Targets and Strategies for Optimization of Response of Solid Tumors

Semin Oncol. 2015 Dec;42(6):801-19. doi: 10.1053/j.seminoncol.2015.09.027. Epub 2015 Sep 24.

Authors

Cinta Hierro¹, Jordi Rodon¹, Josep Tabernero²

Affiliations

¹ Molecular Therapeutics Research Unit, Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
² Molecular Therapeutics Research Unit, Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address: [email protected].

PMID: 26615127
DOI: 10.1053/j.seminoncol.2015.09.027

Abstract

The fibroblast growth factor receptor (FGFR) pathway plays a major role in several biological processes, from organogenesis to metabolism homeostasis and angiogenesis. Several aberrations, including gene amplifications, point mutations, and chromosomal translocations have been described across solid tumors. Most of these molecular alterations promote multiple steps of carcinogenesis in FGFR oncogene-addicted cells, increasing cell proliferation, angiogenesis, and drug resistance. Data suggest that upregulation of FGFR signaling is a common event in many cancer types. The FGFR pathway thus arises as a potential promising target for cancer treatment. Several FGFR inhibitors are currently under development. Initial preclinical results have translated into limited successful clinical responses when first-generation, nonspecific FGFR inhibitors were evaluated in patients. The future development of selective and unselective FGFR inhibitors will rely on a better understanding of the tissue-specific role of FGFR signaling and identification of biomarkers to select those patients who will benefit the most from these drugs. Further studies are warranted to establish the predictive significance of the different FGFR-aberrations and to incorporate them into clinical algorithms, now that second-generation, selective FGFR inhibitors exist.

Publication types

Review

MeSH terms

Antineoplastic Agents / pharmacology*
Biomarkers, Tumor / analysis
Brain Neoplasms / drug therapy
Brain Neoplasms / genetics
Brain Neoplasms / metabolism
Brain Neoplasms / pathology
Breast Neoplasms / drug therapy
Breast Neoplasms / genetics
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Drug Resistance, Neoplasm / drug effects
Drug Resistance, Neoplasm / physiology
Female
Fibroblast Growth Factors / antagonists & inhibitors
Fibroblast Growth Factors / genetics
Fibroblast Growth Factors / metabolism
Gastrointestinal Neoplasms / drug therapy
Gastrointestinal Neoplasms / genetics
Gastrointestinal Neoplasms / metabolism
Gastrointestinal Neoplasms / pathology
Glioblastoma / drug therapy
Glioblastoma / genetics
Glioblastoma / metabolism
Glioblastoma / pathology
Head and Neck Neoplasms / drug therapy
Head and Neck Neoplasms / genetics
Head and Neck Neoplasms / metabolism
Head and Neck Neoplasms / pathology
Humans
Molecular Targeted Therapy / methods*
Neoplasms / drug therapy*
Neoplasms / metabolism
Neoplasms / pathology
Receptors, Fibroblast Growth Factor / antagonists & inhibitors*
Receptors, Fibroblast Growth Factor / genetics
Receptors, Fibroblast Growth Factor / metabolism
Thoracic Neoplasms / drug therapy
Thoracic Neoplasms / genetics
Thoracic Neoplasms / metabolism
Thoracic Neoplasms / pathology

Substances

Antineoplastic Agents
Biomarkers, Tumor
Receptors, Fibroblast Growth Factor
Fibroblast Growth Factors