Histopathological and immunohistochemical comparison of successive implantations of oral squamous cell carcinoma fragments in patient-derived orthotopic graft model

• Grant number: 19/21513-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2019
• Effective date (End): August 14, 2021
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Edgard Graner
• Grantee: Maria Luisa Oliveira Avoletta
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Oral squamous cell carcinoma (OSCC) is the most common head and neck neoplasia and usually affects male patients, over 50 years of age, smokers and alcoholics, with a predilection for the lateral border region of the tongue, mouth floor and lower lip. Despite of all the advance in the knowledge of the OSCC's biology, the survival rates remain around 55% in 5 years, mainly due to high rates of recurrence and metastases. The absence of animal models that mimic the evolution of the disease hinders advances in the development and analysis of the clinical efficacy of new therapies. However, the model of patient-derived xenographic tumor grafts (PDTX) can fill this gap. This model consists of the implantation, orthotopic (PDTX/O) or not, of fragments of solid malignant human neoplasia in immunosuppressed mice and, therefore, presents high fidelity to the complexity and heterogeneity of human tumors and can be used for targeted treatment. In previous studies performed in our laboratory, successive implantations of CEO fragments were established in the PDTX/O model of lateral tongue border. This project aims to analyze and compare the pattern of tumor invasion and the rate of proliferation in the passages of grafts previously performed to determine whether there is a pattern of development that remains faithful or resembles the initial biopsy of the patient. This study will be the basis for the feasibility of future pre-clinical studies for the development and testing of combined therapies aimed at personalization and improvement in the choice of treatment.