September 25, 2019

Lung Cancer Researcher Conducts Clinical Trial for Liquid Biopsies

What will lung cancer diagnosis and treatment look like in the future? Look no further than the research at UAMS that is happening today.

“We’re coming into the long-promised ‘future’ of cancer treatment,” said physician-scientist Donald J. Johann Jr., M.D. “For the last 50 years, the holy grail of cancer research has been being able to detect the presence of cancer with a simple blood test, known as a liquid biopsy, and treat cancer patients on an individualized basis, which is precision medicine.

In pursuit of this quest, Johann was awarded $1.47 million from the Food and Drug Administration (FDA) to continue a clinical trial to develop a liquid biopsy method for diagnosing and monitoring lung cancer.

“Recent advancements in genetic sequencing technology, computational science and the ability to manage massive amounts of data have made this type of research possible,” he said. “The vision is to combine the power of these approaches with clinical knowledge to improve outcomes. This is the future of cancer medicine, and it’s all doable.”

Johann is an associate professor in the departments of Biomedical Informatics and Internal Medicine in the UAMS College of Medicine. Biomedical informatics is a key part of Johann’s work. Its powerful computational methods allow him to process information on a large scale, looking for previously unrecognized patterns.

Johann lab

Donald J. Johann Jr. consults with members of his lab, from left, Meei Liu and Ikjae Shin, Ph.D.

Lung cancer is the leading cause of cancer-related deaths in the United States and the world, and the incidence in Arkansas has been higher than the national average for the past 20 years. Early stage lung cancer is treatable with surgery and chemotherapy and/or radiation, but the cancer often returns after two to three years and is deadly.

Researchers like Johann believe precision medicine is key to changing these statistics.

As an integral part of Johann’s clinical trial, UAMS surgeons provide samples of the tumor at the time of its removal. Back in the lab, Johann’s team runs genetic sequencing on the tumor and re-grows it using different methods. Once the sample tumor is big enough, the team tests individual existing drugs and novel combinations of existing drugs on the tumors to find the most effective treatment.

The information is analyzed and stored so that if that individual patient’s cancer comes back, the doctors will know the best therapies to use. The information is also compiled in large datasets so that researchers can look for aggregate patterns and identify trends regarding which treatments work best for different types of tumors. The goal is for scientists to be able to genetically test a tumor to identify the best course of treatment for that individual patient.

Liquid biopsies are important because the average diagnosis for lung cancer patients is about age 70. Patients are often in poor health in addition to battling cancer, and traditional invasive biopsies can lead to complications or death.

Patients in Johann’s clinical trial give blood samples at multiple stages of treatment. The research team determines whether the cellular material shed by tumors into blood can help doctors detect cancer earlier and monitor patients during cancer treatments to improve outcomes. Again, compiling big datasets plays a role.

The liquid biopsy part of Johann’s lung cancer work is also supported by the Blood Profiling Atlas in Cancer (BloodPAC), a nonprofit consortium for data sharing between stakeholders in industry, academia and regulatory agencies with the goal of making liquid biopsies a reality.

BloodPAC also supports liquid biopsy clinical trials at Memorial Sloan Kettering Cancer Center for prostate cancer, University of Southern California for breast cancer, and University of Pennsylvania for pediatric cancers.

“The collaborative element to this is very important. We work with three very prestigious, NCI-Designated Comprehensive Cancer Centers to accelerate the development of liquid biopsies for cancer treatment guidance and less invasive clinical care,” Johann said. “We want to catch disease early and operate on it for cure, monitor it effectively, develop model systems effectively and then look at potential therapies to see what would be the best treatment for each patient, instead of just giving everyone the standard treatment.

“The practice of clinical oncology is rapidly changing, and we need to be part of that and contribute. When I came to UAMS, I believed we should be able to do state-of-the-art cancer research and treatment here. I’m proud to be part of this science, the teamwork and potential for our patients.”

Johann’s work on lung cancer has been underway for three years. During previous phases, his team developed the advanced bioinformatics and infrastructure at UAMS that are necessary to handle the large datasets involved in this research, and he brought firsthand knowledge of the latest molecular technologies to UAMS.

UAMS is working to achieve National Cancer Institute (NCI) Designation for its Winthrop P. Rockefeller Cancer Institute, which would benefit Arkansans with improved access to clinical trials and expanded access to federal research funding. Research like Johann’s is both part of that effort to gain designation and an example of what will be possible – on an even larger scale – once designation is achieved.