HDAC Inhibitors in Cancer Therapy

Overview

Without exception, metastasis rates kill nearly 90% of cancer patients (Gupta and Massague 2006). The process of metastasis is not yet fully understood, but it is strongly linked to the loss of some proteins such as CD29, CD44, and E-cadherin, E-cadherin is a protein that holds the cells together. It is indispensable for the proper organization of tissues and organs in our body. When cancer cells lose the function of this protein during the tumor development process, tumor cell deorganization occurs – the tumor cells then change shape and motility and transform to invasive cells

Two models attempt to explain the development of tumor metastases. The genetic model is based on mutations of the genome that accumulate in the rapidly growing cells and lead to the development of a metastatic cell phenotype. The epigenetic development model relies mainly on changes in gene expression that can not be attributed to changes in the DNA nucleotide sequence

HDACI for Cancer Treatment

Histone deacetylase (HDAC) inhibitors constitute a new group of epigenetic agents that has gained much attention in drug development in cancer

  • Suberoylanilide hydroxamine (Vorinostat)
  • LBH589 (Panobinostat)
  • Valproate (VPA)

The modification of methylation or the acetylation provide a new therapeutic approach to the Anti-metastatic therapy.

Epigenetic Inhibition of Tumor Metastasis

The inhibition of cell migration and invasion is a major goal of the new metastasis-inhibiting therapies to increase the chances of survival for patients with metastatic disease. The study of epigenetic relationships in the field of cell migration and tumor cell metastasis is intended to promote the understanding of the malignant behavior of tumor cells and to help in the development of novel ways in cancer therapy. The present project investigates mechanisms associated with inhibition of cell motility, invasion and migration in cancer cells.