Targeting cancer metastasis through isoform selective HDAC inhibitors

• Grant number: 19/01173-2
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: April 01, 2019
• End date: June 30, 2019
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Flavio da Silva Emery
• Grantee: Letícia Bueno de Oliveira
• Supervisor: Arasu Ganesan
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of East Anglia (UEA), England
• Associated to the scholarship: 18/10418-6 - Synthesis of a library of benzothiazolinic derivatives for the evaluation of inhibition of Leishmania major dihydroorotate dehydrogenase, BP.IC

Abstract

Heritable changes in gene expression that are not based upon alterations in the DNA sequence are defined as epigenetics. The most common mechanisms of epigenetic regulation are the N-terminal histone tails. In the last years, it became evident that the onset of cancer and its progression may not occur only due to genetic mutations but also because of changes in the patterns of epigenetic modifications. In contrast to genetic mutations, which are almost impossible to reverse, epigenetic changes are potentially reversible.This implies that they are amenable to pharmacological interventions. Recently, epigenetic regulation has been shown to play a role in cancer cell migration and invasion through the action of histone deacetylase (HDAC) enzymes, particularly some isoforms. Our objective is to design potent and selective inhibitors of these isoforms, and explore their ability to inhibit cell migration. These compounds will be novel leads that selectively target the cell migration process while avoiding the side effect profile observed with non-selective clinically approved HDAC inhibitors. (AU)