An epigenetic cure for cancer?

A review article by researchers at the Boston University School of Medicine suggests that subtle changes in DNA expression patterns could be targeted to treat cancer, reducing the risk of cancer relapse. The authors, led by Sibaji Sarkar, PhD, propose that chemical modification of DNA and the negatively charged proteins it binds to – ultimately resulting in changes in gene expression and cell phenotype – plays a role in driving cancer stem cell formation. Whilst our current understanding of these “epigenetic” changes remains sketchy, the hypothesis developed by Sarkar and colleagues may represent an important leap forward in the field of cancer research.

One in three people in the UK will develop cancer in their lifetime. Cancer exists in several forms, but broadly consists of a complex disease characterised by unchecked cell proliferation and tissue invasion. Many scientists believe that cancer develops from perverted immortal progenitor cells. The immortality of these “cancer stem cells” is believed to underlie both tumours’ resistance to chemotherapy and their relapse.

Sarkar and colleagues propose that gene silencing by DNA methylation – in conjunction with other genetic and environmental events – could trigger cancer stem cell formation. Over-expression of the enzyme responsible for DNA methylation in cancer cells is believed to silence genes that promote cell death and prevent tumour growth. On the contrary, oncogenes – genes with the potential to cause cancer – are highly expressed in cancer cells. The authors hypothesise that this bizarre mis-match is the result of concurrently active DNA methylating and demethylating enzymes found only in cancer cells. Current epigenetic drug treatments are believed to facilitate gene demethylation, increasing the expression of anti-growth genes.

At present, the role of epigenetic changes in cancer development is poorly understood. Despite this, it is clear that epigenetic drugs could eliminate cancer stem cells and generate vast improvements in patient outcomes and relapse rates.