Related Experiment Video
Updated: Jun 13, 2026
Lateral Molar Approach-Driven Transoral Endoscopic Procedure for Benign Infratemporal Fossa Tumor Resection
Published on: August 15, 2025
Are we on the brink of nonsurgical treatment for ameloblastoma?
John J Sauk1, Nikolaos G Nikitakis, Mark A Scheper
1School of Dentistry, University of Louisville, Louisville, KY 40201, USA. john.sauk@louisville.edu
Objective:
Recent identification of altered molecular signaling pathways in neoplasia has begun to elucidate mechanisms of oncogenesis, differentiation, and tumor progression, and to suggest plausible nonsurgical considerations for treatment. Here we review the sonic hedgehog (SHH) and PI3K/Akt/mTOR signaling pathways, their role in ameloblastoma, a locally aggressive odontogenic tumor, and evidence for consideration of therapeutic approaches that target these molecular pathways. In so doing, some of the gaps will be revealed that may impel investigations and translate to patient care, helping to minimize or eliminate the need for extensive surgery.
Study Design:
This is a comprehensive review of the literature regarding alterations in signaling mechanisms associated with ameloblastomas. In addition, this review attempts to explore and discuss possible inhibitors to these pathways that may have utility in treating ameloblastoma.
Results:
The expression of SHH signaling molecules in ameloblastomas at the mRNA and protein levels has intimated that these molecules may play a role in cell proliferation of these tumors. Immunohistochemical analysis has revealed aberrant signaling in the PI3K/Akt/mTOR pathway in ameloblastomas and appears to be a valuable tool for elucidating pathogenesis and aggressiveness, and selecting optimal therapeutics.
Conclusion:
The understanding of altered pathways in ameloblastoma may soon provide nonsurgical options for the treatment of this condition. The demonstration of cross talk in SHH signal transduction with PI3K signaling through Akt has shown that these pathways converge to control the Gli transcription factors. Thus, tumors that entirely depend on active SHH signaling for survival/growth and maintenance may well be susceptible targets for combined chemotherapy with SHH-specific inhibitors together with PI3K, Akt, or mTOR blocking agents. Some of these inhibitors could be used locally, thereby minimizing major systemic effects.
Insights
Targeting the Sonic Hedgehog (SHH) and PI3K/Akt/mTOR pathways offers potential nonsurgical treatments for ameloblastoma. Combined therapies inhibiting these pathways may reduce tumor growth and the need for extensive surgery.
Area of Science:
- Oncology
- Molecular Biology
- Pathology
Background:
- Neoplasia involves altered molecular signaling pathways crucial for oncogenesis and tumor progression.
- Ameloblastoma, a locally aggressive odontogenic tumor, exhibits dysregulated molecular signaling.
- Targeting these pathways presents potential nonsurgical therapeutic strategies.
Purpose of the Study:
- To review the role of Sonic Hedgehog (SHH) and PI3K/Akt/mTOR signaling pathways in ameloblastoma.
- To explore evidence for therapeutic approaches targeting these molecular pathways.
- To identify research gaps for improved patient care and reduced surgical intervention.
Main Methods:
- Comprehensive literature review on signaling mechanism alterations in ameloblastomas.
- Exploration and discussion of potential pathway inhibitors for ameloblastoma treatment.
Main Results:
- SHH signaling molecules are expressed at mRNA and protein levels in ameloblastomas, suggesting a role in tumor cell proliferation.
- Aberrant PI3K/Akt/mTOR pathway signaling is identified in ameloblastomas via immunohistochemistry.
- Immunohistochemical analysis aids in understanding ameloblastoma pathogenesis, aggressiveness, and therapeutic selection.
Conclusions:
- Altered molecular pathways in ameloblastoma may lead to future nonsurgical treatment options.
- SHH and PI3K signaling converge on Gli transcription factors, indicating potential for combined therapy.
- Targeting SHH, PI3K, Akt, or mTOR with specific inhibitors, potentially used locally, could treat ameloblastomas effectively with minimized systemic effects.