Glioblastoma kills fast. Median survival is only 12 to 16 months from diagnosis, even with aggressive treatment, said Huali Su of the Ohio State University Comprehensive Cancer Center. Two separate research teams now say that knocking out a single enzyme can stop cancer growth in lab models of hard-to-treat tumors.
Prostate cancer that stops responding
Researchers at Sanford Burnham Prebys report that prostate cancer can be killed by blocking an enzyme called PI5P4Kα. The work appeared in Science Advances.
Most prostate cancers can be held back with drugs that lower testosterone and other male sex hormones. But about 10 to 20 percent resist treatment within five years. The cancer then spreads through the body and becomes deadly.
The idea began in Bern. Colleagues of Brooke Emerling at the University of Bern, led by Mark A. Rubin, noticed that patients with treatment-resistant disease had high levels of the enzyme. Emerling’s team then used several prostate cancer model systems to show that inhibiting it killed resistant tumors.
“What’s remarkable is that we’ve found an enzyme that can be targeted against prostate cancer even in cases where treatments that lower hormones are ineffective or where resistance has developed,” said Emerling, an associate professor at Sanford Burnham Prebys. She expects it to matter in other cancers too, such as breast, skin and pancreatic.
There is no drug yet. “I have high hopes that in the near future, we’ll have something in clinical trials,” she said.
A different enzyme in brain tumors
A study from Ohio State, also in Science Advances, looked at glioblastoma. Su and colleagues wrote that therapy for the disease has shown no substantial change in 20 years.
Earlier work focused on an enzyme called GFAT1, which is overexpressed in nearly 90 percent of glioblastoma samples from patients. Blocking it did little. The tumors got around it by using a second route to keep making the same compounds.
The Ohio State team found that targeting PGM3 shuts down both routes at once. In mouse models, that suppressed tumor growth and extended median survival from 23 to 29 days. PGM3 was elevated in more than 83 percent of patient tissue samples.
“Blocking the PGM3 enzyme can break the connection between sugar and fat creation in cells, which helps stop tumors from growing,” said Delian Guo, director of the university’s Center for Cancer Metabolism and lead author. Inhibiting PGM3 has also suppressed growth in breast and pancreatic tumors and some lung cancers. The authors cautioned that no one target will work across all cancers in this pathway.
Sources
- Targeting single enzyme has potential for drug resistant prostate cancer – ecancer
- New Enzyme Target Shows Promise to Stop Glioblastoma Growth
