The role of HDAC6 in the regulation of oxidative stress and chemoresistance of cancer stem cells in oral carcinoma

Abstract

Chemoresistance is a major cause of failure in cancer therapy, increasing the risk of metastasis. Chemoresistance is initiated by a small group of cells identified as cancer stem cells. In oral carcinoma, the cancer stem cell population is accumulated after chemotherapy, and epigenetic modifications may be controlling this process. HDAC6 is a histone deacetylase found accumulated in cancer stem cells. HDACs are a group of deacetylase enzymes that epigenetically regulate chromatin organization and gene expression by removing acetyl groups from lysine residues in histones and nonhistone proteins. HDAC6 acts in several physiological processes, including oxidative stress response, autophagy and DNA damage response, and its accumulation is associated to the development of pathological disorders, such as cancer. Establishing efficient therapeutic strategies in cancer treatment is important to understand the epigenetic factors that promote chemoresistance, as well as exploring the behavior of tumor stem cells and the signaling that regulates their metabolism. This project aims to investigate the role of HDAC6 in the tumor resistance process mediated by cancer stem cells in oral carcinoma, evaluating the influence of HDAC6 on the DNA damage response and oxidative stress and its possible application as a potential therapeutic target to eliminate cancer stem cells and reverse chemoresistance. (AU)