Cancer can be defined as an abnormal proliferation of cells that defy the normal regulatory controls observed by normal cells. Recently, histone deacetylation therapies have been attempted in the treatment of certain cancers [reviewed by Delcuve et al. (2009)]. Specifically, the FDA has approved histone deacetylation (HDAC) inhibitors for the treatment of cutaneous T-cell lymphoma. Explain why histone acetylation might be associated with cancer and what the rationale is for the use of HDAC inhibitors in the treatment of certain forms of cancer.

Key Concepts

Histone Acetylation

Histone acetylation is a post-translational modification where acetyl groups are added to the lysine residues on histone proteins. This modification reduces the positive charge on histones, leading to a more relaxed chromatin structure that promotes gene expression. In cancer, abnormal patterns of histone acetylation can result in the activation of oncogenes or the silencing of tumor suppressor genes, contributing to uncontrolled cell proliferation.

Histone Deacetylases (HDACs)

Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histones, leading to a more compact chromatin structure and reduced gene expression. Overactivity of HDACs can result in the repression of genes that normally inhibit cell growth and promote apoptosis, thereby facilitating cancer progression. Targeting HDACs with inhibitors can restore normal gene expression patterns and induce cancer cell death.

HDAC Inhibitors in Cancer Therapy

HDAC inhibitors are a class of drugs that block the activity of histone deacetylases, leading to increased acetylation of histones and a more open chromatin structure. This can reactivate silenced tumor suppressor genes and enhance the expression of pro-apoptotic factors, making them effective in treating certain cancers, such as cutaneous T-cell lymphoma. The rationale for their use lies in their ability to reverse the epigenetic changes associated with cancer and restore normal cellular functions.