TY - JOUR
T1 - Fibroblast Growth Factor (FGF) Receptor/FGF Inhibitors
T2 - Novel Targets and Strategies for Optimization of Response of Solid Tumors
AU - Hierro, Cinta
AU - Rodon, Jordi
AU - Tabernero, Josep
N1 - Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
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U2 - 10.1053/j.seminoncol.2015.09.027
DO - 10.1053/j.seminoncol.2015.09.027
M3 - Review article
C2 - 26615127
AN - SCOPUS:84962308189
SN - 0093-7754
VL - 42
SP - 801
EP - 819
JO - Seminars in oncology
JF - Seminars in oncology
IS - 6
ER -