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Updated: May 9, 2026
07:50
Establishment of a Clinic-based Biorepository
Published on: May 29, 2017
FGFR2 signaling underlies p63 oncogenic function in squamous cell carcinoma
Matthew R Ramsey1, Catherine Wilson, Benjamin Ory
1Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, Massachusetts, USA.
The Journal of Clinical Investigation
|July 23, 2013
Summary
Squamous cell carcinoma (SCC) relies on the transcription factor p63 for survival. Targeting p63-driven FGFR2 signaling with AZD4547 effectively regresses established SCC tumors, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- Oncogenic transcription factors are key drivers of human cancers.
- Squamous cell carcinoma (SCC) outcomes have seen limited improvement due to poor understanding of its molecular pathogenesis.
- SCCs often overexpress the p53-related transcription factor p63.
Purpose of the Study:
- To investigate the function of p63 in SCC pathogenesis.
- To identify key transcriptional programs regulated by p63 in SCC.
- To explore therapeutic targeting of p63-driven pathways in SCC.
Main Methods:
- Development of an in vivo murine tumor model for SCC.
- Acute genetic ablation of p63 in established, invasive SCC.
- In vivo genome-wide gene expression analysis.
- Inhibition of FGFR2 signaling using the clinical inhibitor AZD4547.
Main Results:
- Established SCCs are critically dependent on p63.
- p63 ablation led to rapid tumor regression and apoptosis.
- A p63-regulated tumor-survival program involving FGFR2 signaling was identified.
- Paracrine FGFR2 signaling, activated by stromal ligands, supports SCC growth.
- AZD4547 demonstrated therapeutic efficacy against endogenous SCCs.
Conclusions:
- p63 plays an essential role in SCC survival and progression.
- p63-driven paracrine FGFR2 signaling is an "addicting" pathway in SCC.
- Targeting the p63-FGFR2 axis represents a promising therapeutic strategy for SCC.
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