Evaluation of silencing of overexpressed genes in cisplatin-tolerant A549 lung adenocarcinoma cells

• Grant number: 24/14902-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Roger Chammas
• Grantee: Pedro Henrique Fernandes Gatti
• 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

Lung cancer is the neoplasia responsible for the highest number of deaths in Brazil and worldwide. Several therapeutic approaches for non-small cell lung cancer (NSCLC), its most common type, are based on chemotherapy with combinations of cisplatin, a drug with cytotoxic potential that acts by causing DNA damage. However, the efficacy of cisplatin is limited due to the development of tumor tolerance. From a single-cell gene expression analysis conducted by our laboratory, comparing cisplatin-sensitive and -tolerant cells, a gene signature related to cisplatin tolerance was identified. With the aim of developing a new therapeutic approach based on reconfigurable nucleic acid nanoparticles (recNANPs) capable of delivering multiple small interfering RNAs (siRNAs), different combinations of these genes were tested, looking for the ones that, when overexpressed, had the greatest impact on patient prognosis. Therefore, as an initial step in the development of therapeutic recNANPs, the goal of this project is to test the efficacy of siRNAs for silencing genes included in the selected combinations in lung cancer cell lines, and to evaluate the impact of this silencing on the cisplatin tolerance phenotype.