Delivering hope

Joo Ha Hwang was often the first person to tell people they had pancreatic cancer. It was hard for him to deliver this news because he knew this was a lethal diagnosis and his patients would die within the year. Hwang, a clinical gastroenterologist, came to the UW after medical school to work at the UW Medical Center and earn a Ph.D. in bioengineering. While working, he saw an unmet clinical need for treatment options for patients with pancreatic cancer and decided to address the problem through research. Hwang and his team are now using ultrasound technology to test drug delivery methods in mice. They’re hoping this could lead to new discoveries in curing one of the deadliest cancers. Pancreatic cancer is hard to detect, Hwang said, and once doctors are able to detect it, the cancer is usually in the very late stages and has spread to other organs. Ninety-five percent of patients diagnosed with pancreatic cancer will not be alive five years after their diagnosis. Most live less than a year, according to the National Center for Biotechnology Information. Typical cancer treatments, like chemotherapy, are not effective in pancreatic cancer because of the type of tumor. Pancreatic-cancer tumors have a unique cell structure, said Navid Farr, a bioengineering researcher who is pursuing a Ph.D. It’s a dense, fibrous tissue that has very few blood vessels. So when drugs are administered through the body, they often do not penetrate into the tumor. Farr is part of the small group of professionals, graduate students, and undergraduate students who comprise Hwang’s team. The team is part of the Center for Industrial and Medical Ultrasound (CIMU) in the Applied Physics Lab (APL). Hwang, Farr, and the other researchers are trying to find new ways to get into the tumor and treat the cancer without harming the rest of the body. Their Old Fisheries Building lab is equipped with ultrasounds to monitor the drugs in the tumor. Here, they also study the more basic mechanics of drug delivery methods. They also work in a lab at South Lake Union where they use a magnetic resonance imaging (MRI) machine equipped with high-intensity focused ultrasound (HIFU). The HIFU machine is a normal Phillips brand MRI machine with a special table top that has a HIFU transducer, Farr said. “It focuses the ultrasound beam at the focal point and it has higher intensity and higher energy level,” Farr said. “So without damaging any tissue, or anything in between, you can deposit energy at the focus, which causes heat, like a magnifying glass.” Once the researchers locate the tumor in the mouse model using HIFU, they push the temperature-sensitive liposome (TSL) chemotherapy-containing drug into the tumor. To do this, they keep the area in a state of mild hyperthermia. Farr said scientists speculate that hyperthermia allows blood flow or enhances permeability of tissue. This aids when trying to treat the dense pancreatic tumor tissue. This drug delivery method is important because it stops the toxic chemotherapy from going throughout the body; instead, it goes directly into the tumor. This prevents some of the chemotherapy side effects, Farr said, like hair loss. “[This method] will increase the efficacy while decreasing the toxicity of the drugs,” Hwang said. What the team calls a “mouse model” is not a typical mouse to be found in a pet store. Instead, it is an expensive, genetically modified mouse called KPD. Each letter stands for a different genetic modification. The model was developed by Hwang’s collaborators Sunil Hingorani and David Tuveson when they both worked at the University of Pennsylvania. Hwang said this is the most reliable model for pancreatic-cancer research. The reason this specific model is so vital, Farr said, is because unlike other mouse models, it exactly mimics the tissue structure of the human disease. “In this case we can say that whatever we are doing will be so similar to human disease, so if this method is effective it will be a good chance this method will be effective in human disease,” he said. Once they have completed their study, Farr said they “sacrifice” the mouse and collect samples from the tumor and other areas of the body to check, both quantitatively and qualitatively, for the drug. They have been successful so far with these delivery methods. It has allowed them to get concentrations of five to eight times the amount of drug into the tumor of their mouse model, compared with traditional delivery methods, Hwang said. The team is now ready to move on to survival studies. This means they will monitor how long the mouse model survives and track whether the cancer was affected by the treatment. Yak-Nam Wang, a senior engineer for CIMU who is working on the project with Hwang, said the survival studies are an important step in the research. “It’s important to see both safety and efficacy,” she said. “It’s fair enough if we can see an increase in drug penetration but we don’t know if that amount of drug is enough to kill the cancer cells, so we need these survival studies to see if the treatments are successful in killing cancer cells and stopping tumor growth.” Hwang hopes to be done with survival studies by next fall. Then, he said, he will approach the Food and Drug Administration (FDA) about doing pilot trials in humans. There are a lot of regulations in place that make human trials challenging, Hwang said, and the team has to worry about getting funding, which they will gather from within the industry, the government, and different philanthropic routes. But he said he is very confident about bringing the research into human trials. These would likely last around five years. For Hwang, it isn’t just about being successful in his research. It’s about creating a treatment method that he, and other doctors who deal with pancreatic cancer, can use. “I’ve always wanted to tell a patient, ‘But we have this therapy that we can treat you with’ so it would be very rewarding to have done research and come up with a therapy,” Hwang said. “By doing research you have the ability to potentially impact many more patients than you could treat individually, so it would be incredibly rewarding to see this technology and this method to treat patients with pancreatic cancer. We’ll see if it makes it.” Reach Features Editor Sarah Radmer at science@dailyuw.com. Twitter: @sarahradmer Corrections: David Tuveson was inaccurately identified. Tuveson is not a collaborator of Joo Ha Hwang's. The name of the mouse model was also inaccurately identified. The mouse model the research team uses is a KPC model.

Delivering hope

Disruptor interrupts Psych 210, professor and students chase man on to Red Square

2025 Seattle and King County primary election endorsements

UW mechanical engineering students are now required to pay $250 quarterly fee to participate in department-affiliated RSOs

College Inn Pub reopens under new ownership