New research from Stanford University reports insights on how a rare genetic disease known as NGLY1 deficiency could help scientists understand how some drug resistance works. The research article can be found in yesterday's ACS Central Science.
Currently, many blood cancers are being treated with proteasome inhibitors. These inhibitors work by stopping the cancer cell machinery and eventually induce cell death. However, the cancer cells have learned to develop resistance to these inhibitors by turning on a protein called Nrf1. Nrf1 goes into overdrive and works to restore the cells' normal activities.
In this study, Carolyn Bertozzi and colleagues were studying NGLY1 deficiency and found that NGLY1 is responsible for activating Nrf1. By dampening NGLY1, the researchers were able to see that the proteasome inhibitors were able to remain effective without interference from Nrf1.
The authors believe that there is great promise in this work for the development of combination therapeutics for blood cancers in the future.
Image: A protein called Nrf1 (shown in white in these mouse cells) can hamper promising drugs for blood cancers, but now researchers have found a possible workaround to shut Nrf1 down. Image courtesy of The American Chemical Society.