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Exploring the Horizon: Anti-Fibroblast Growth Factor Receptor Therapy in Pancreatic Cancer with Aberrant Fibroblast
Elena Orlandi1, Massimo Guasconi2,3, Stefano Vecchia4
1Department of Oncology-Hematology, Azienda USL of Piacenza, 29121 Piacenza, Italy.
Abstract:
Pancreatic cancer is a highly lethal disease, often diagnosed at advanced stages, with a 5-year overall survival rate of around 10%. Current treatments have limited effectiveness, underscoring the need for new therapeutic options. This scoping review aims to identify and summarize preclinical and clinical studies on FGFR (Fibroblast Growth Factor Receptor) inhibitors, including tyrosine kinase inhibitors (TKIs) and FGFR-specific inhibitors, in pancreatic cancer with FGFR alterations. We included studies analyzing efficacy, safety, and survival outcomes in various populations. A comprehensive search across major databases identified 73 relevant studies: 32 preclinical, 16 clinical, and 25 from gray literature. The clinical trials focused primarily on efficacy (20 studies) and safety (14 studies), with fewer studies addressing survival outcomes. FGFR1 was the most studied alteration, followed by FGFR2 and FGFR4. Although FGFR alterations are relatively rare in pancreatic cancer, the available data, including promising real-life outcomes, suggest significant potential for FGFR inhibitors. However, more extensive research is needed to identify the correct genetic drivers and gather robust survival data. Ongoing and future trials are expected to provide more comprehensive insights, potentially leading to improved targeted therapies for pancreatic cancer patients with FGFR alterations.
Insights
Fibroblast Growth Factor Receptor (FGFR) inhibitors show promise for pancreatic cancer patients with specific genetic alterations. Further research is needed to confirm survival benefits and optimize targeted therapy strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pancreatic cancer has a poor prognosis with limited effective treatments.
- Fibroblast Growth Factor Receptor (FGFR) alterations occur in a subset of pancreatic cancers.
- Targeted therapies are needed for this aggressive malignancy.
Purpose of the Study:
- To conduct a scoping review of preclinical and clinical studies on FGFR inhibitors in pancreatic cancer.
- To summarize efficacy, safety, and survival data for FGFR-targeted therapies.
- To identify research gaps and future directions for FGFR inhibition in pancreatic cancer.
Main Methods:
- Comprehensive literature search of preclinical and clinical studies.
- Inclusion of studies analyzing efficacy, safety, and survival outcomes.
- Systematic review of 73 relevant studies from databases and gray literature.
Main Results:
- Fibroblast Growth Factor Receptor 1 (FGFR1) was the most frequently altered and studied.
- Clinical trials primarily focused on efficacy and safety, with limited survival data.
- Available data suggest potential efficacy of FGFR inhibitors, especially in real-world settings.
Conclusions:
- FGFR inhibitors represent a potential targeted therapy for pancreatic cancer with FGFR alterations.
- More research is required to identify predictive biomarkers and gather robust survival data.
- Ongoing and future clinical trials are crucial for advancing FGFR-targeted treatment strategies.
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