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In 2020, approximately 42,810 adults in the U.S. will be diagnosed with liver cancer, a number that is currently on the rise. The most common type of liver cancer is Hepatocellular carcinoma (HCC), which makes up approximately 75% of all liver cancer cases. More than half of patients with liver cancer are diagnosed after the disease has advanced – meaning the cancer has spread outside the liver. For those whose cancer has spread to distant parts of the body, only 2% are alive five years after diagnosis. Clearly, there is an urgent need for new treatments to improve clinical outcomes.

Each year, the American Society of Clinical Oncology (ASCO) brings together oncology professionals from around the world to collaboratively share the latest research and data in all areas of oncology, including HCC. Dr. Katie Kelley, a gastrointestinal oncologist and associate professor of clinical medicine at UCSF researching the early development of new treatments and biomarkers in HCC and cancers of the biliary tract, shares her insights on the status and advancement of the HCC therapeutic landscape.

What is HCC?

Dr. Kelley: The liver is a complex organ that plays a central role in human metabolism. Most of the functions of the liver are carried out by cells called hepatocytes, which are epithelial cells lining the sinusoids of the liver. When exposed to conditions which cause cellular injury, hepatocytes can undergo malignant transformation to become HCC, the most common type of liver cancer and a cancer with very poor prognosis. In the U.S., leading causes of liver injury causing HCC are non-alcoholic fatty liver disease and hepatitis C virus. Hepatitis B virus is a leading cause of HCC worldwide. Other causes of liver injury resulting liver fibrosis and cirrhosis, such as excessive alcohol use, also can cause HCC. Alarmingly, the death rate from liver cancer has more than doubled between 1980 and 2017, and liver cancer is now the fastest rising cause of cancer-related death in the U.S. In recent years, the great need for more effective treatments for HCC has spurred a broad range of research across stages.

What is the current treatment landscape for HCC?

Dr. Kelley: Treatment options for HCC depend on the stage of the cancer, whether the surrounding liver has fibrosis or cirrhosis, and the patient’s overall health. Surgery is the standard treatment when HCC is detected early, if the rest of the liver is healthy, and offers the best chance of a cure. If the rest of the liver is too unhealthy for surgery, liver transplantation can also be a curative option some patients if the cancer is detected at early stages. However, many patients don’t develop any signs and symptoms until the disease has advanced, meaning that by the time they are diagnosed the disease has already spread outside the liver to nearby structures such as the blood vessels within the liver —and in some cases outside the liver to lymph nodes or other organs. At this point, few treatment options are available. Identification of effective treatments has remained one of the biggest challenges in HCC, which has proven to be a particularly difficult to treat cancer. Standard chemotherapies have not been effective in HCC, due in part to chemoresistance of the liver to conventional chemotherapies, as well as to the toxicity of chemotherapy in people with underlying liver dysfunction.

Fortunately, researchers are continuing to work to learn more about HCC, how to best treat it, and how to provide the best care to people diagnosed with HCC . In the past few years, we have seen these efforts yield unprecedented progress, with the advent of new treatments beyond standard chemotherapy for HCC.

What research or other developments make you optimistic about the future of HCC treatment?

Dr. Kelley: Most patients with liver cancer are either diagnosed with or progress to advanced stages of disease during their diagnosis. While HCC remains an incredibly difficult cancer, scientists and researchers across the field, including my colleagues and I, are working hard to better understand the biology of HCC to find new, safe, and effective treatment options for our patients. So, the good news is that there is an enormous amount of important research underway. It has been so encouraging to see the promise of the emerging data and the directions ahead I’m very optimistic about the future of treatment given the advances we’re seeing today with targeted therapies, immunotherapy, and the rational combinations of these agents, and I truly believe patients facing this difficult disease have more reasons to be hopeful now than ever before.

R. Kate (Katie) Kelley, MD, is Associate Professor of Clinical Medicine, Department of Medicine, University of California, San Francisco.