Investigation of the antineoplastic potential of pharmacological inhibition of ezrin in solid tumors: gastric adenocarcinoma and cervical carcinoma

• Grant number: 22/14505-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2023
• End date: August 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: João Agostinho Machado Neto
• Grantee: Maria Fernanda Lopes Carvalho
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer, one of the most debilitating diseases in the world, is characterized by an exacerbated and disordered proliferation of cells, which can invade adjacent tissues and spread to other organs. Cervical carcinoma is the fourth most common cancer in women and treatment options for the advanced stage are limited, leading to high mortality, while gastric cancer is the fifth most common in the world and has an overall 5-year survival rate of about from 25% to 30%. Drugs that act on the cytoskeleton have high toxicity due to their low selectivity. Thus, the identification of molecules that are differentially expressed in physiological and neoplastic conditions is of paramount importance in the search for new potential therapeutic targets. The ezrin protein, encoded by the EZR gene, acts in multiple cellular processes including proliferation, survival and motility, through signal transduction between membrane receptors and the actin cytoskeleton. Literature data indicate a relevant role for this protein in the malignant phenotype of cancer cells, however its role in the prognosis is not fully elucidated in patients with cervical cancer. In view of the above, the present research project aimed to characterize the antineoplastic potential of pharmacological inhibition of ezrin in gastric and cervical cancer cell lines, in addition to investigating the impact of EZR expression on survival outcomes, clinical characteristics and functions. in TCGA cohort patients with these solid tumors.