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Oncotarget. 2017 Feb 28;8(9):16052-16074. doi: 10.18632/oncotarget.14109.

Inhibition of the fibroblast growth factor receptor (FGFR) pathway: the current landscape and barriers to clinical application.

Author information

1
Developmental Therapeutics Program of the Division of Hematology Oncology, Chicago, IL, USA.
2
Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA.
3
Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
4
Dana Farber Cancer Institute, Boston, MA, USA.
5
Division of Hematology Oncology, University of Alabama Birmingham, Birmingham, AL, USA.

Abstract

The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) is a tyrosine kinase signaling pathway that has a fundamental role in many biologic processes including embryonic development, tissue regeneration, and angiogenesis. Increasing evidence indicates that this pathway plays a critical role in oncogenesis via gene amplification, activating mutations, or translocation in tumors of various histologies. With multiplex sequencing technology, the detection of FGFR aberrations has become more common and is tied to cancer cell proliferation, resistance to anticancer therapies, and neoangiogenesis. Inhibition of FGFR signaling appears promising in preclinical studies, suggesting a pathway of clinical interest in the development of targeted therapy. Phase I trials have demonstrated a manageable toxicity profile. Currently, there are multiple FGFR inhibitors under study with many non-selective (multi-kinase) inhibitors demonstrating limited clinical responses. As we progress from the first generation of non-selective drugs to the second generation of selective FGFR inhibitors, it is clear that FGFR aberrations do not behave uniformly across cancer types; thus, a deeper understanding of biomarker strategies is undoubtedly warranted. This review aims to consolidate data from recent clinical trials with a focus on selective FGFR inhibitors. As Phase II clinical trials emerge, concentration on patient selection as it pertains to predicting response to therapy, feasible methods for overcoming toxicity, and the likelihood of combination therapies should be utilized. We will also discuss qualities that may be desirable in future generations of FGFR inhibitors, with the hope that overcoming these current barriers will expedite the availability of this novel class of medications.

KEYWORDS:

factor; fibroblast; growth; inhibition; receptor

PMID:
28030802
PMCID:
PMC5362545
DOI:
10.18632/oncotarget.14109
[Indexed for MEDLINE]
Free PMC Article

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