Oral carcinoma tumor microenvironment in young patients: a multimodal study to identify novel therapeutic targets

• Grant number: 24/16703-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2025
• End date: February 29, 2028
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Lidia Maria Rebolho Batista Arantes
• Grantee: Bianca Cruz Pachane
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

The oral squamous cell carcinoma (OSCC) is a highly aggressive and lethal neoplasm that typically affects the tongue and the floor of mouth in males, smokers and over 50-year-old individuals. The recent rising incidence of OSCC in younger patients (< 40 years old) is altering the lesion epidemiological profile and challenging its treatment. Immunotherapy is the standard or second-line treatment for aggressive OSCC, differently from the current treatment approved by the Brazilian Unified Health System (SUS) with chemotherapy and radiotherapy combination. In this project we propose to investigate the differences in tumor microenvironment of OSCC lesions in younger patients (<40 years old) compared to older patients (>40 years old) to search for new potential therapeutic targets. Initially, we propose to evaluate the combined proteome, metabolome and transcriptome of tumor samples from patients to detect potentially altered pathways and components. We intend to evaluate the tumor microenvironment of young OSCC patients by culturing primary cells in 2D and 3D to develop spheroids and organoids and developing co-culture models with tumor microenvironment cells. Finally, we suggest evaluating the in vitro responses to combination therapy with cisplatin, 8 Gy radiotherapy, anti-PD-1 and/or anti-PD-L1 immunotherapy, assessing cell viability, motility, morphology, and extracellular vesicle (EV) secretion. Results will be compared with clinical data and tumor behavior before and after combination therapy, validated in the institution's retrospective case study and contrasted with in silico results from older OSCC patients. This study aims to identify potential therapeutic targets for OSCC in young patients and provide solid preclinical evidence of the therapeutic efficacy for this type of lesion.