Sphingolipids in oral cancer: microenvironment, therapy response and therapeutic strategies

• Grant number: 25/04347-2
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2025
• End date: October 31, 2028
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Andréia Machado Leopoldino
• Grantee: Andréia Machado Leopoldino
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• City of the host institution: Ribeirão Preto

Abstract

Oral cancer is a highly aggressive and immunosuppressive disease, associated with high global mortality rates, largely due to insufficient understanding of the molecular mechanisms that control its progression and resistance to conventional treatments. Through innovative studies, our research group has identified sphingolipids (SPs) as key molecules in promoting more aggressive tumor phenotypes, associated with unfavorable disease prognoses. However, the main molecules in this group, such as sphingosine-1-phosphate (S1P) and ceramides, have not yet been adequately validated from a translational perspective, which hinders progress in the development of more effective therapies. Considering this, this project aims to investigate and validate the mechanisms by which these molecules modulate the tumor microenvironment, with an emphasis on macrophage differentiation, and how they impact critical cellular processes such as extracellular vesicle release, energy metabolism, angiogenesis, metastasis, and treatment response. To achieve this, we will adopt an integrated approach combining in vitro (cell cultures), in vivo (zebrafish), and ex vivo (human samples) experimental models, aiming to elucidate the roles of these molecules in promoting more aggressive tumor phenotypes and their clinical-scientific impact. Therefore, this study hypothesizes that specific sphingolipid molecules, previously identified by our group, play a crucial role in promoting more aggressive phenotypes in oral cancer, and that a deeper understanding and validation of these molecules as biomarkers, therapeutic targets, and modulators of treatment response could open new avenues for more effective and personalized treatments, driven by an innovative translational approach. Given the importance of the topic and the necessity to foster sustainable healthcare practices, this project also suggests the establishment of a university extension initiative designed to increase awareness about the production and appropriate disposal of chemical and healthcare waste, especially that generated from chemotherapy treatments, along with activities focused on prevention and early diagnosis of head and neck cancer. (AU)