The role of the transcription factor STAT1 in radio and chemoresistance in tumors of the oral cavity and oropharynx: epidemiological and functional approach.

• Grant number: 25/12575-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2025
• End date: July 31, 2029
• Field of knowledge: Health Sciences - Collective Health - Epidemiology
• Principal Investigator: Laura Cristina Sichero Vettorazzo
• Grantee: Letícia Torres Barboza
• Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). São Paulo , SP, Brazil
• Associated research grant: 24/13024-0 - Cellular transcription factors as prognostic biomarker and therapeutic target in tumors induced by human papillomavirus 16 (HPV-16)., AP.R

Abstract

Persistent infections with high-risk oncogenic HPV (human papillomavirus) have been associated with cancer development since the early 1970s. The prevalence of HPV in oropharyngeal carcinoma (OPC) ranges from 10% to 70%, depending on the geographic region. Among these cases, type 16 is present in almost all tumors attributed to HPV. In general, the stage and extent of head and neck tumors determine the treatment strategy, which may include surgery, radiation, chemotherapy, or a combination of these approaches. Despite significant advancements, tumor resistance to these treatments is commonly observed.The cellular phenotype is ultimately determined by gene expression patterns, which regulate critical cellular functions such as survival, proliferation, and self-renewal. It is known that the activity of transcription factors (TFs), which coordinate gene expression, is highly regulated. In the context of persistent HPV-16 infections, it is reasonable to propose that many of the TFs regulating viral expression and consequently, the levels of the viral oncoproteins E6 and E7, may influence the clinical outcomes of HPV-related diseases.In this project, we aim to conduct an integrated epidemiological and functional assessment of the roles of STAT1 and PARP as prognostic biomarkers and therapeutic targets for HPV-16-induced tumors. We hypothesize that high STAT1 expression combined with low PARP1 expression contributes to HNSCC (head and neck squamous cell carcinomas), and that modulating the levels of these proteins results in differential responses to treatment with RT/QT, whether concomitant or not. We believe that these findings open new opportunities for the development of personalized treatments for patients affected by HNSCC.