Altering the body’s metabolism could be an effective treatment for deadly liver cancer, researchers report.
The finding that inhibiting heat shock transcription factor 1, or HSF1, prevents liver cancer in mice is also another wake-up call that a low-fat, healthy diet is an effective cancer deterrent, says Demetrius Moskophidis, MD, cancer virologist/immunologist at Georgia Health Sciences University. HSF1 and its target genes are important to metabolism regulation.
“The principle that we demonstrated is that if we change the metabolism, we can interfere with tumor growth,” says Moskophidis, co-corresponding author on the study.
GHSU scientists accomplished this by removing HSF1 from the mice; HSF1 inhibitors are under development because of their potential for treating a variety of other cancers such as breast, prostate, and kidney cancers. Removing HSF1 thwarts liver cancer by decreasing access to two critical elements: glucose and lipids.
Tumors use glucose for energy as well as the rapid cell division essential to cancer growth, says Xiongjie Jin, MD, GHSU assistant research scientist and the study’s first author. Lipids are needed in cancer and for new cells, to make membranes so those cells can communicate. Lipids also serve as an additional energy source.
Mice lacking HSF1 are hypersensitive to glucose, able to efficiently turn it into energy that can be used by the body so little can be diverted to cell division, says Nahid Mivechi, MD, director of the GHSU Center for Molecular Chaperone, Radiobiology, and Cancer Virology and the study’s corresponding author.
The mice also produce fewer lipids because they easily make active protein kinase (AMPK) which helps regulate energy levels and inhibits lipid synthesis, Moskophidis says, adding, “lipid-hungry tumors don’t like AMPK.”
The studies were done in genetically altered mice that were later exposed to a carcinogen known to produce cancer in 100% of male mice within five to seven months. Now the scientists are removing HSF1 from mice that already have cancer to see if this approach—which better reflects how treatment would be used in humans—works as well.