Some things always seem better in combos: beer & pizza, SpongeBob & square pants… Soon, we may need to add Vidaza® & entinostat to that list. At the recent American Society of Clinical Oncology annual meeting, researchers from Johns Hopkins Medical Institute and the Lovelace Respiratory Research Institute reported that the combination of Vidaza® (5-azacitidine) and entinostat (SNDX-275) has significant activity in patients with advanced relapsed non–small cell lung cancer (NSCLC). For those that might not be familiar with brand names…
- Vidaza® is an inhibitor of DNA methyltransferase (DNMT) and is FDA approved for treating myelodysplasia.
- Entinostat is an oral inhibitor of histone deacetylase (HDAC) that was developed in Japan back in the ‘90s but has studied by several research teams since.
One of the primary drivers behind the current testing of entinostat with Vidaza® in lung cancer is that “epigenetic gene silencing mediated through aberrant DNA methylation and histone deacetylation is a key contributor to lung carcinogensis.” This point is also echoed in another recent study which shows how miR-143 acts as an endogenous inhibitor of DNMT3a in colorectal cancer.
These studies suggest that there may be a role for entinostat in combination with other agents for the treatment of a wide variety of tumors, and highlight the critical role of epigenetics in disease.