It seems like almost every gene examined today has it roots in cancer, and epigenetic mechanisms haven’t missed the invite to that party. But with all these players comes an overwhelming heterogeneity that has troubled researchers looking for a cure ever since cancer was described as an epigenetic disease. Some research groups have tried out global disruptors of the epigenome, like the DNA methylation inhibitor 5aza-2deoxycytidine, but they’ve all come across the same problem. The inhibitors aren’t very specific. In fact, much like the U.S. government’s budget sequester, they are quite ubiquitous and cause a plethora of global issues.
So in order to gain some insight into cancer treatment, a group of researchers from Université de Nantes (France) brainstormed novel ways to attack the problem. Rather than just inhibit DNMT1, they designed peptides to interfere with specific interactions between DMNT1 and other key proteins involved in the epigenetic landscape. Here’s what they found:
- 5aza-2deoxycytidine, procainamide or peptides disrupting the DNMT1/PCNA, DNMT1/EZH2, DNMT1/HDAC1, DNMT1/DNMT3b and DNMT1/HP1 interactions promoted or enhanced in vivo tumorigenesis in a mouse glioma model.
- Interestingly, a peptide disrupting the DNMT1/DMAP1 interaction (“which per se did not affect tumor growth”) sensitized cancer cells to chemotherapy.
- The peptide disrupting the DNMT1/DMAP1 interaction also increased the efficiency of temozolomide treatment.
Ultimately, this research highlights a new frontier in cancer treatment and suggests, “that the targeting of certain DNMT1/protein-x interactions opens a new area in the development of targeted epigenetic therapy”.
Check out the DNMT1 disruptions in Clinical Epigenetics, June 2013.