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Liver cancer is the third leading cause of cancer-related death worldwide. Most of the time, liver cancer is diagnosed at a later stage because it doesn’t show symptoms early on. Advanced liver cancer is harder to treat, and Huntsman Cancer Institute (HCI) researcher and pathologist Kimberley Evason, MD, PhD, says we need more treatment options. Here, she explains the liver cancer research her lab is doing to understand how tumors form and whether antidepressants could possibly prevent or shrink liver tumors.
Why is it hard to find liver cancer early?
Symptoms of liver cancer don’t usually appear early on. You can’t see your liver from the outside, so it’s not like skin cancer, where there’s a lesion on your skin. A lot of cancers cause pain or a blockage or, with colon cancer, blood in your stool. With liver cancer, a lot of patients don’t have symptoms or don’t until it’s more advanced.
In addition, a lot of patients don’t know they have liver disease so they don’t know they’re at high risk. There are currently no standard screening tests for liver cancer, although liver cancer screening tests are being studied in clinical trials.
How do tumors form in the liver?
The vast majority of patients who get liver cancer have cirrhosis, or end-stage liver disease. Cirrhosis is scaring of the liver that prevents blood to flow as it should. This is most often caused by heavy, ongoing alcohol use or chronic hepatitis infection. When the liver gets injured over time, it gets damaged. As a response to that damage, liver cells have to grow more. They try to make up for the cells killed by inflammation or disease. When cells grow and divide more, that can predispose you to getting cancer because cells aren’t meant to rapidly divide like that.
How could antidepressants affect liver cancer?
My lab is focused on β-catenin, a protein that helps transmit signals within cells. In many liver cancers, β-catenin is transmitting abnormal signals that help the cancer to grow and survive. Our most interesting work is doing drug screening in zebrafish (small, transparent fish often used in cancer research). If we find a drug that can suppress β-catenin liver overgrowth in fish, meaning we’re able to shrink the liver in the fish, we hope we can prevent or shrink a tumor in a human with cancer.
The drug we’ve discovered that, so far, shows the most promising result is an antidepressant called amitriptyline that decreases liver size in our zebrafish model. My lab is trying to figure out how these antidepressants are working before we try to use them in people. We think antidepressants are inhibiting serotonin signaling, perhaps by decreasing serotonin levels in the liver. Serotonin promotes cell proliferation (cells growing and dividing), so if you inhibit serotonin signaling, you should get less proliferation of liver cancer cells.
You and your colleagues have discovered higher amounts of a certain kind of fat in liver cancer cells. How does this fat impact the disease?
We aren’t sure yet how or why this fat impacts the disease, but we are working to figure that out. Some types of fat are involved in transmitting signals within cells, so one possibility is that increases in this fat disrupt this signaling process and promote cells to divide more (thus causing tumors to grow).
What can people do to prevent liver cancer?
About 80–90% of liver cancers occur in people with cirrhosis. So one way to prevent liver cancer would be to prevent chronic liver disease:
- Maintain a normal weight (to prevent non-alcoholic fatty liver disease).
- Drink alcohol only in moderation.
- Get vaccinated for hepatitis B.
- Avoid infection by or seek treatment for hepatitis C.
If you already have cirrhosis, it is important to get tested regularly for liver cancer. This is typically done through imaging tests and/or blood tests. If liver cancer is diagnosed early, it is much easier to treat with surgery or radiation.
Learn more about risk factors for liver cancer.