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Combatting Liver Cancer

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Liver cancer is one of the fastest-growing causes of cancer death in the U.S. and in many other parts of the world, says Mark Yarchoan, co-director of the Liver Cancer Multidisciplinary Clinic. Since the new liver cancer clinic launched a little more than a year ago, they have seen a more than 500% increase in patient volume. A team of Johns Hopkins medical oncologists, interventional radiologists, radiation oncologists, surgeons, radiologists, pathologists, palliative care specialists, and research nurses are collaborating to change the trajectory of liver cancers through pioneering laboratory and clinical research.

Fibrolamellar hepatocellular carcinoma (FLC), a very rare form of liver cancer that usually affects children and young adults and has no standard treatment, is an active area of clinical research. Yarchoan says. He and colleague Marina Baretti developed a vaccine that may help the body’s immune system recognize FLC tumors. They are studying the use of this new vaccine in combination with two other immunotherapies, nivolumab, and ipilimumab. This will be the first clinical trial to specifically target the gene that drives FLC, he says.

Nilofer Azad, co-director of the Clinic, and Yarchoan are working together on a national trial that studies the drugs cobimetinib, a MEK inhibitor, in combination with the immunotherapy atezolizumab in bile duct cancer (also called cholangiocarcinoma). The initial results, which demonstrated that the combination delayed tumor progression when compared to atezolizumab alone, were presented at this year’s annual meeting of the American Association for Cancer Research.

MEK inhibitors may make immunotherapies work better through an interaction among cancer cells and immune cells, but work on preclinical models and on clinical samples from the trial suggest that MEK inhibition may cut both ways, Yarchoan explains. MEK inhibitors increase the number of immune cells in the tumor, but they also make these immune cells less active. His laboratory is studying whether the addition of other immunotherapies could rescue T cell activation and make this treatment combination work better.

The Liver Cancer Multidisciplinary Clinic is also pioneering a new approach to treating hepatocellular carcinoma (HCC), the most common form of liver cancer. Curative surgery is the ideal treatment but often not an option, Yarchoan says. Most liver cancers recur after surgery, he says.

In a new approach, Yarchoan and collaborators are using a combination of targeted therapy and immunotherapy to try to shrink liver cancers, potentially allowing patients with locally advanced or inoperable cancers to eventually go to surgery and reducing the chances that these cancers come back. This treatment approach of immunotherapy before surgery was pioneered at the Kimmel Cancer Center for lung cancer with results so promising that it is being studied in several other cancer types. By the time of surgery, many patients see their tumors disappear or significantly diminished in size.