Role of purinergic signaling in doxorubicin resistance in triple-negative breast cancer

• Grant number: 25/14273-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2025
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Claudiana Lameu
• Grantee: Ana Carolina Galdino Picolli
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence ofhormone receptors and HER2, which limits therapeutic options and is associated with high ratesof metastasis, recurrence, and chemoresistance. Studies indicate that the acquisition of aGABAergic phenotype by TNBC cells may promote brain colonization, and that purinergicsignaling mediated by P2X7 and P2Y2 receptors is also involved in this process, as well ascontributing to treatment resistance. This project aims to investigate the interaction betweenchemoresistance, the GABAergic phenotype, and purinergic signaling in TNBC cells.Chemoresistance will be induced in vitro through cyclic treatment with doxorubicin intumorspheres of the MDA-MB-231 parental and MDA-MB-231-BR cell lines. Subsequently,cell viability in response to treatment will be evaluated, as well as the expression of markersrelated to the GABAergic and purinergic systems. It is expected that the integrated analysis ofthese systems will provide a better understanding of the molecular mechanisms associated withTNBC progression and resistance, contributing to the development of more effective therapies. (AU)