A Promising Alternative Therapy for Advanced Liver Cancer Patients

A lymphotoxin-beta receptor inhibitor may stop the spread of the disease.

Blocking a key immune receptor may stop the spread of liver cancer, the results of a recent study found.

The Sanford Burnham Prebys Medical Discovery Institute (SBP), the National Cancer Institute, and the Chulabhorn Research Institute collaborated on the study to identify more viable treatment options for liver cancer patients.

"Cancers of the hepatobiliary system, including cholangiocarcinoma and hepatocellular carcinoma, typically present in advanced stages, with impaired liver function, respond poorly to chemotherapy, and have poor survival based on the lack of available treatment options," said Paul Timothy Fanta, MD, associate clinical professor in the Division of Hematology and Oncology at UC San Diego's Moores Cancer Center."

Carl Ware, PhD, first identified lymphotoxin-beta receptor (LTβR) as vital in controlling lymphoid organs and regulating inflammation. The researchers found that blocking the receptor's activity reduces inflammation.

In other studies, LTβR was elevated in liver cancer patients where higher levels of the receptor lead to poorer survival rates. An LTβR-inhibitor could be a useful alternative to chemotherapy for patients with advanced liver cancer, the researchers found.

"For some time we have known about the interconnection between the receptor, inflammation -- including inflammation caused by hepatitis -- and liver cancer,” Ware said. “Now, we have demonstrated how the receptor's signals create an environment that accelerates oncogenic activity and tumor growth.”

In the study, mice infected with AKT/β-catenin or AKT/Notch liver cancer progressions were observed after receiving either an LTβR activator (agonist) or an inhibitor (antagonist). In the mice treated with the agonist, liver cancer progressed rapidly. In mice treated with the antagonist, however, tumors reduced and survival improved.

"Our findings point to a new way to improve the treatment of liver cancer patients," Ware added. "Combining drugs that are currently in clinical trials, which block the activity of the LTβR with drugs that target oncogene signals, may be a valuable new approach to improving patient outcomes."

This study was published in the online edition of Gut.