Spatial transcriptome in advanced oral cavity squamous cell carcinoma and response to treatment: modulation by cancer-associated fibroblasts and in vitro validation

• Grant number: 24/20525-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2025
• End date: January 31, 2029
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Camila de Oliveira Rodini Pegoraro
• Grantee: Emanuelle Pangoni de Carvalho
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

Oral squamous cell carcinoma (OSCC) is an aggressive and heterogeneous tumor, with an overall survival rate that has remained stagnant at 50% over recent decades. Notably, even in advanced OSCC stages (III and IV), there can be both responsive and refractory patients, for whom there is no therapeutic option that promotes significant tumor remission in the majority of cases, especially within the public health system. In this context, it is important to investigate tumor components and the tumor microenvironment (TME), and consequently, the biological mechanisms involved in therapeutic success or failure. Based on this, a deeper study of the molecular and proteomic profiles of both tumor cells and cancer-associated fibroblasts (CAFs) in advanced OSCC may be promising and provide potential therapeutic targets to benefit this specific group of patients. Therefore, this project aims to locate, characterize, and spatially quantify molecular targets in different regions of the tumor and TME (using GEOMX¿ DSP, Nanostring) in advanced OSCC, in patients responsive and refractory to treatment (surgery, chemo, and radiotherapy), and subsequently validate these targets using tissue samples (immunohistochemistry) and multicellular spheroids (qPCR and immunofluorescence). For in vitro assays, two OSCC cell lines (SCC-9 and HSC-3) will be used in 3D co-culture with CAFs. Ultimately, this study aims to identify prognostic biomarkers that could serve as potential therapeutic targets in advanced OSCC, especially in treatment-refractory patients. (AU)