Introduction to epigenetics

 

Cancer is a disease where certain cells have escaped from the normal and very tight controls that usually regulate cell growth and behaviour. Using a traffic analogy, normal cells follow the prescribed traffic rules and obey the speed limits, whereas cancer cells are renegade drivers who no longer follow any road rules, often go “off road” and cause accidents and pile ups with no regard for the consequences.

Traditionally we treat cancer using chemotherapy to eliminate the cancer cell population while keeping as many normal cells as possible. That is, we try and take the bad drivers off the road.  Chemotherapy typically aims to permanently damage the DNA of cancer cells and cause widespread death of these cells.  However, usually a small number of cancer cells evade the effects of chemotherapy, and these persistent cancer cells are often more aggressive and go on to eventually cause cancer recurrence.  This in part explains why chemotherapy loses its effectiveness over time. 

Epigenetics refers to a mechanism that reversibly influences gene (DNA) expression without altering DNA sequences, and thus offers a way to “reprogram” cancer cells back towards a normal cell type. Or using our traffic analogy, epigenetics seeks to re-educate cancer cells to once again follow the road rules.  

As such epigenetic treatment could be used during and after chemotherapy to treat the persisting cancer cells and hopefully extend the duration of cancer remission and improve cancer patient survival. Epigenetic treatment could also be used prior to chemotherapy to re-educate cancer cells to minimise the number of aggressive cells requiring further intervention.

EpiAxis is therefore exploring an epigenetic approach to the treatment of cancer by developing specific inhibitors against LSD1 with its lead molecules such as EPI-111. LSD1 is an epigenetic enzyme which functions to control transcriptional events on histones and whose overexpression has been correlated with poor prognosis in a variety of cancers.