Investigation of the prognostic impact of PIP4K2s and their pharmacological inhibition in hepatocellular carcinoma

• Grant number: 23/12969-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2024
• End date: July 31, 2028
• 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, occurs due to an exacerbated and disorderly proliferation of cells, which can infiltrate adjacent tissues and spread to other organs. Hepatocellular carcinoma is the most common liver neoplasm, the 5th most common type of cancer and one of the main causes of cancer-related death in the world. The identification of molecules that are differentially expressed in physiological and neoplastic conditions is extremely important in the search for new, more selective therapeutic targets in this context. Studies have shown that the double inhibition of PIP4K2A and PIP4K2B proteins reduces in vitro cell survival of breast cancer cells and the formation of tumors in mice -, which drew attention to the importance of this family in the development of cancer. Recently, high-resolution genomic data were generated by The Cancer Genome Atlas (TCGA) from samples of cancer patients and deposited in public databases, which represents a valuable opportunity for exploration through statistical and bioinformatics tools. Given the above, the present research project aimed to investigate the impact of PIP4K2s expression on survival outcomes, clinical characteristics and biological functions in patients with hepatocellular carcinoma from the TCGA cohort, in addition to characterizing the antineoplastic potential of pharmacological inhibition of PIP4K2s , in experimental models of hepatocellular carcinoma.