Fibroblast Growth Factor Receptors: From the Oncogenic Pathway to Targeted Therapy

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Fibroblast growth factors (FGFs) and their receptors (FGFRs) are key regulators of cell proliferation, migration, differentiation, and survival.
• Deregulation of the FGF/FGFR signaling pathway, through mechanisms like gene mutations, fusions, and amplification, is implicated in various cancers.
• While diagnostic tests exist for FGFR1, FGFR2, and FGFR3 abnormalities, an ideal molecular diagnostic assay remains elusive.

Purpose of the Study:

• To review genomic alterations in the FGF/FGFR pathway associated with solid tumors.
• To discuss molecular diagnostic assays for stratifying patients for FGFR-targeted therapies.
• To highlight the development of therapeutic drugs targeting the FGF/FGFR pathway.

Main Methods:

• Review of literature on FGF/FGFR pathway genomics in solid tumors.
• Analysis of DNA and RNA-based technologies for detecting FGFR abnormalities.
• Examination of preclinical and clinical data for FGFR-targeted therapeutics.

Main Results:

• Genomic alterations in FGFR1, FGFR2, and FGFR3 are significant drivers in solid tumors.
• Various DNA and RNA-based assays are employed for detecting these alterations, though none are universally optimal.
• Therapeutic strategies including tyrosine kinase inhibitors (TKIs) and anti-FGFR monoclonal antibodies are under investigation.

Conclusions:

• Understanding FGF/FGFR pathway genomic alterations is critical for cancer diagnosis and treatment.
• Development of precise molecular diagnostic assays is essential for patient stratification.
• Targeted therapies offer promising avenues for treating cancers with aberrant FGF/FGFR signaling.