LRH-1 Inhibitors Show Promise Treating Liver Cancer

Mice without the LRH-1 protein develop less liver cancers than mice who had the protein.

A recent study found that blocking the protein liver receptor homolog 1 (LRH-1) prevents liver cancer cells from getting the glutamine they need to survive, which essentially starves them.

LRH-1 breaks glutamine into smaller molecules consumed by liver cancer cells, which become addicted to the amino acid, according to the study published in Genes & Development. Researchers genetically modified mice to not have the LRH-1 protein, and found they created less liver tumors after being exposed to carcinogens compared with mice who express LRH-1.

"Shutting down this pathway by inhibiting LRH-1 abrogates the utilization of glutamine as a fuel and brings the cancerous cells in tremendous metabolic distress," said study first author Xu Pan.

The researchers believe their study could provide a new treatment target for liver cancers.

"Inhibiting LRH-1 can thus be an effective way to starve only liver cancer cells, while leaving normal cells intact," said lead researcher Kristina Schoonjans, PhD.

Researchers are now evaluating new chemotherapies to treat liver cancer through creating LRH-1 inhibiting compounds, and hope their findings can be used for other cancers that have high expression of LRH-1, the study concluded.