When cancer spreads, the liver is one of its favorite go-to targets.

It’s the most common site for metastases from cancers of the pancreas and colon. When prostate cancer spreads, it travels to the liver almost 25% of the time.

"Metastatic liver cancer is not well-studied, but it’s a serious health threat," says Shelly Lu, MD, director of the  Karsh Division of Gastroenterology and Hepatology  at Cedars-Sinai and the Women’s Guild Chair in Gastroenterology. "When cancer spreads to the liver, it’s often terminal."

Survival rates after liver cancer metastasizes vary based on many factors, including the cancer’s origin. Of people with colon cancer that spreads to the liver, 89% will die within five years. For pancreatic cancer patients in the same situation, 97% die within five years.

A team of investigators led by Lu launched a five-year study of liver cancer metastases, funded by a $9.1 million grant from the National Cancer Institute at the National Institutes of Health. It’s the first study in the history of those organizations to bring together multiple scientists studying this problem from various angles.

A common thread in the four studies is the different roles that fat might play in promoting liver cancer metastases. One study investigates how a high-fat diet alone could promote cancer, even in a healthy liver.

Another approach looks to the hepatocytes, the most plentiful type of liver cell. The study will explore the behavior of these cells when they contain excess fat, as observed in people who have fatty liver disease. “How are these fatty cells making the liver more hospitable to cancer?” is the big question Lu and colleagues are trying to answer. 

A third project will investigate metastases from pancreatic cancer and a specific signaling pathway—a chain reaction of molecules that controls how cells behave. This particular pathway is common in pancreatic cancer and is more common when the liver is fatty. Understanding these pathways is often a crucial step in developing targeted therapies.

Lu also is studying proteins that are usually plentiful in the liver but are scarce in people with nonalcoholic fatty liver disease.

"Our hope is that through this collaboration, studying all these different aspects of liver metastases, we will be able to figure out how that leads the cancer to the liver to set up shop," Lu says.