SCREENING FUNCTIONAL REGULATORS OF G0 ARREST-PROLIFERATION DECISIONS USING SIRNA

• Grant number: 25/05833-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 31, 2025
• End date: August 30, 2026
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marcelo Bispo de Jesus
• Grantee: Thais de Moraes Lacerda
• Supervisor: Alexis Ruth Barr
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Imperial College London, England
• Associated to the scholarship: 22/09246-1 - Phenotypic profiling based on high content analysis applied to the development of therapeutic strategies for dormant breast cancer cells, BP.DR

Abstract

Breast cancer is the most prevalent malignancy among women and the second most common cancer globally, with tumor recurrence being a significant factor in poor patient outcomes. Despite advances in early detection and treatment, recurrence remains a major therapeutic challenge, often occurring years after initial therapy. A key mechanism underlying recurrence is tumor cell dormancy, where cells enter a quiescent state, evading conventional therapies and contributing to disease relapse. This dormancy state is characterized by G0 arrest, where cells exit the cell cycle, enhancing their resistance to chemotherapy. The molecular mechanisms regulating G0 arrest in breast cancer cells are poorly understood, partly due to the lack of reliable biomarkers and experimental models. Traditional markers like Ki67 and CDK2 fail to effectively distinguish G0 from other non-proliferative states, limiting their utility in studying quiescence. Recent studies have identified gene signatures associated with quiescence, but these associations do not establish causal relationships between specific genes and G0 regulation. This project aims to elucidate the molecular mechanisms of G0 arrest in breast cancer by employing siRNA-mediated gene knockdown and high-content imaging. By integrating these approaches, we aim to identify key genetic regulators of G0 entry and reactivation, providing insights into the biological processes of cancer dormancy. The goal is to uncover therapeutic targets that can prevent recurrence and improve clinical outcomes for breast cancer patients. Ultimately, this research seeks to develop novel strategies to eliminate dormant tumor cells, thereby reducing recurrence and enhancing long-term survival rates. (AU)