A feedback loop between the androgen receptor and 6-phosphogluoconate dehydrogenase (6PGD) drives prostate cancer growth
© KATERYNA KON/SCIENCE PHOTO LIBRARY/Getty Images
New strategies for treating prostate cancer could come from the discovery of a metabolic pathway that prostate cancer cells use to grow and survive.
Cancer cells often use different cellular metabolisms from healthy cells.
Now, a team by led researchers at the University of Adelaide has shown that prostate tumours often express high levels of an enzyme called 6-phosphogluoconate dehydrogenase (6PGD). This enzyme activates an alternative pathway for sugar metabolism and produces antioxidants that help make cells resistant to standard hormone deprivation therapies.
The team found that tumour growth was suppressed by drugs that inhibit 6PGD.
6PGD is also activated by signalling through the androgen receptor targeted by hormone deprivation therapies, which helps explain why combination drug regimens directed at both 6PGD and the androgen receptor seem to have especially pronounced anti-tumour effects.
A plant-derived compound that inhibits 6PGD has been evaluated for safety in human volunteers. The researchers propose testing this agent, or other 6PGD blockers, in clinical trials for prostate cancer.
- eLife 10, e62592 (2021). doi: 10.7554/eLife.62592