Prospecting biomarkers of response to antineoplastic agents and molecular and clinical-laboratory correlation in acute lymphoblastic leukemia using an ex vivo platform

• Grant number: 24/02796-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2024
• End date: April 30, 2027
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eduardo Magalhães Rego
• Grantee: Keli Cristina de Lima
• Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The research project aims to develop an ex vivo platform to assess the effectiveness of drugs in samples from adult patients with acute lymphoblastic leukemia (ALL) within the context of a clinical study. The goal is to correlate drug responses with genetic, proteomic, metabolic, and clinical-laboratory characteristics. Peripheral blood and bone marrow samples from ALL patients diagnosed at the Cancer Institute of the State of São Paulo will be collected and processed. ALL cells will be cultured in co-culture with immortalized human mesenchymal stem cells to evaluate the response to experimental drugs such as THZ-P1-2, AD80, NSC305787, NT157, among others, and clinically approved reference drugs. Drug responses will be assessed by flow cytometry and correlated with gene expression and global proteomic data and metabolic profile analysis. The project involves multidisciplinary collaborations, combining clinical hematology and cellular and molecular pharmacology. The main challenge is to integrate bedside research with laboratory investigations, increasing the levels of evidence related to the compounds of interest. The objective is to develop a precision medicine platform in onco-hematology and validate new anticancer agents for treating ALL in adults, overcoming scientific and technological challenges. The project may contribute to scientific innovation and the development of more effective treatments for ALL.