Battling Cancer by Targeting Epigenetics

Cancer is a devastating disease that exists in different forms and can vary from patient to patient. Ultimately this multidimensional disease causes healthy cells to lose their ability to reproduce at healthy rates. Scientists at Temple University’s School of Medicine have identified a positive trend in cancer cases when inhibiting a specific gene, CDK9. Inhibiting this transcription regulator gene with the drug MC180295 reactivated tumor suppressor genes that were epigenetically silenced in cases of cancer. When CDK9 is active, it functions as a transcription regulator and also inhibits the activity of BRG1, which is recognized for its role in DNA repair mechanisms as well as replication and transcription processes. Application of MC180295 ultimately resulted in increased tumor suppressor gene activity and healthy cell division, both in vitro and in vivo.

Genes that are epigenetically modified do not have alterations in their actual DNA sequence, but are rather silenced due to a methylated cytosine base pair, histone protein modifications, or other modifications at the gene’s site that prevent the gene from expression. In cancer cases, BRG1 is epigenetically silenced by CDK9 and cells lose critical regulation functions.

This gene was identified as a gene of interest through a live cell drug screen that screened cancer lines with different drug samples. This treatment discovery was viewed as a breakthrough because it is the first to link CDK9 to other silenced genes. The drug utilized was also highly selective in inhibiting the specific CDK9 site, thus making BRG1 more active in regulating transcriptional processes. This would also avoid potential damage to the cell cycle in functioning cells that is observed in contemporary cancer treatments. It would be interesting to see if any risk factors are associated with inhibiting CDK9. Because of CDK9’s role as a transcription regulator, observing cell activity in the absence of this gene will help strengthen the case for this drug's utility moving forward.