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Updated: Oct 7, 2025
Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
Published on: January 31, 2025
Targeting hedgehog signaling in pancreatic ductal adenocarcinoma
Delphine Quatannens1, Yannick Verhoeven1, Peter Van Dam2
1Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp, Antwerp, Belgium.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer related death. The urgent need for effective therapies is highlighted by the lack of adequate targeting. In PDAC, hedgehog (Hh) signaling is known to be aberrantly activated, which prompted the pathway as a possible target for effective treatment for PDAC patients. Unfortunately, specific targeting of upstream molecules within the Hh signaling pathway failed to bring clinical benefit. This led to the ongoing debate on Hh targeting as a therapeutic treatment for PDAC patients. Additionally, concurrent non-canonical activation routes also result in translocation of Gli transcription factors into the nucleus. Therefore, different downstream targets of the Hh signaling pathway were identified and evaluated in preclinical and clinical research. In this review we summarize the variety of Hh signaling antagonists in different preclinical models of PDAC. Furthermore, we discuss published and ongoing clinical trials that evaluated Hh antagonists and point out the current hurdles and future perspectives in the light of redesigning Hh-targeting therapies for the treatment of PDAC patients.
Insights
Pancreatic ductal adenocarcinoma (PDAC) treatments face challenges due to aberrant hedgehog (Hh) signaling. This review explores Hh antagonists in PDAC models and clinical trials, discussing future strategies for effective Hh-targeting therapies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer mortality with limited therapeutic options.
- Aberrant activation of the hedgehog (Hh) signaling pathway is implicated in PDAC development and progression.
- Previous attempts targeting upstream Hh molecules have yielded insufficient clinical benefits, necessitating alternative strategies.
Purpose of the Study:
- To review hedgehog (Hh) signaling antagonists in preclinical PDAC models.
- To discuss the efficacy and challenges of Hh antagonists in ongoing and completed clinical trials for PDAC.
- To explore future perspectives and potential redesign of Hh-targeting therapies for PDAC.
Main Methods:
- Literature review of preclinical studies evaluating Hh signaling antagonists in PDAC models.
- Analysis of published and ongoing clinical trials assessing Hh antagonists in PDAC patients.
- Synthesis of data to identify current hurdles and future directions in Hh-targeted therapy.
Main Results:
- Various Hh signaling antagonists have demonstrated efficacy in preclinical PDAC models.
- Clinical trials investigating Hh antagonists have shown mixed results, highlighting challenges in therapeutic application.
- Non-canonical activation routes and downstream targets represent areas for further investigation.
Conclusions:
- Despite challenges, Hh signaling remains a potential therapeutic target in PDAC.
- Redesigning Hh-targeting strategies, possibly focusing on downstream effectors or combination therapies, is crucial.
- Further research is needed to overcome current hurdles and develop effective Hh-based treatments for PDAC.
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