Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling

Area of Science:

• Oncology
• Molecular Biology
• Cancer Signaling Pathways

Background:

• Targeted cancer therapies are context-dependent, influenced by tumor signaling pathways and cell-type crosstalk.
• The Fibroblast Growth Factor (FGF)/FGF receptor (FGFR) signaling axis is a key example of context-dependent signaling in cancer.
• Aberrant FGFR signaling is prevalent across numerous cancer types, including lung, breast, glioblastoma, prostate, and gastrointestinal cancers.

Purpose of the Study:

• To review the role of Fibroblast Growth Factor (FGF)/FGF receptor (FGFR) signaling in cancer.
• To highlight the context-dependent nature of FGFR signaling in cancer progression.
• To explore the diverse signaling partners and mechanisms of FGFR in cancer.

Main Methods:

• Literature review of studies on FGF/FGFR signaling in various cancers.
• Analysis of genetic aberrations (amplification, overexpression, mutations, translocations) in FGFR1-4.
• Investigation of canonical and noncanonical FGFR signaling pathways and interactions.

Main Results:

• FGFR signaling is frequently dysregulated in cancer, primarily via FGFR1 and FGFR2 amplification/overexpression leading to ligand-independent activation.
• Mutations and translocations of FGFR1-4 are also implicated in cancer development.
• Noncanonical interactions with cell adhesion molecules, extracellular matrix proteins, and other receptor tyrosine kinases contribute to cancer cell invasion, migration, angiogenesis, therapy resistance, and metastasis.

Conclusions:

• FGFR signaling plays a significant role in cancer progression through both canonical and noncanonical pathways.
• The diverse interactions of FGFR with various cellular components underscore its importance in cancer, irrespective of direct genetic alterations.
• Understanding FGFR signaling complexity is vital for developing effective, context-aware targeted cancer therapies.