Versiti investigators are harnessing research to improve treatment options and patient outcomes.
When most people hear the words “precision medicine,” cancer typically comes to mind. The idea is to match each patient with the medication that best treats his or her illness. Unfortunately, such treatments are not widely available, and most patients diagnosed with cancer often rely on chemotherapy which, in addition to killing cancer cells, also kills the healthy cells that patients need to keep their strength up.
But scientists like Versiti Blood Research Institute (BRI) Associate Investigator Sid Rao, MD, PhD, are making strides in cancer research to understand how cells mutate differently in individual patients and cause cancer. “It’s always been driven by the concept that if we can find a specific mutation that causes this cancer, we can give each patient a specific drug,” he said.
Dr. Rao believes that the best way to understand the genetics behind leukemia, a cancer of blood cells, is to use next-generation sequencing, which takes small bits of a patient’s DNA and analyzes it to determine which mutations cause leukemia to develop. Though Dr. Rao and his peers are confident they know which mutations are key players, it will take much more time to understand the sequences and combinations of these mutations.
Working alongside Dr. Rao in examining genetic mutations is Associate Investigator and Medical Director for Versiti Comprehensive Center for Bleeding Disorders Lynn Malec, MD, MSc. As a hematologist, her work focuses on patients with bleeding disorders like hemophilia, but she is interested in learning how Dr. Rao’s techniques could be used to treat patients with bleeding disorders. Dr. Malec said that currently, there are three primary treatment options for patients with bleeding disorders: 1) putting in a central line to continuously replace the factor concentrates that a patient is missing; 2) start factor replacement gradually, with the patient visiting a clinic on a regular basis; or 3) non-factor therapy, which involves giving the patient medicine subcutaneously (by injection under the skin), similarly to how diabetics give themselves insulin shots.
The trouble is, about 30% of patients with severe hemophilia end up developing an immune response to their factor replacement, which means they can no longer receive it. By looking at each patient’s underlying genetics, Dr. Malec said, “We might be better able to understand who’s at risk for developing an inhibitor and start them on subcutaneous treatment without even giving them factor infusions. Other patients might be very unlikely to develop an inhibitor, and we can start them on factor therapy right away.”
Like Dr. Rao, Associate Investigator Nan Zhu, PhD, also researches the genetics behind leukemia, though she takes a different approach. She focuses on epigenetic regulators, which regulate the changes in cells without affecting the cells’ underlying DNA. “Our research aims to identify therapeutic targets in acute myeloid leukemias with a specific genetic underpinning, namely leukemias with a rearranged MLL gene,” she said. “We have identified a protein called JMJD1C that is important in this type of leukemia, and therefore a potential therapeutic target.”
Using genetics isn’t the only way to analyze mutations and develop new treatments. BRI Investigator Weiguo Cui, MD, PhD, studies T cells, components of the immune system that typically protect us from everyday illnesses like minor viral and bacterial infections. T cells are highly energized when they are up against short-lived illnesses like the flu; however, in patients with extended illnesses like cancer, T cells become exhausted and are rendered ineffective. Dr. Cui is interested in finding a way to re-energize these T cells and kick-start their disease-fighting powers. “We intend to harness the power of one’s own immune system to fight cancer,” he said. “This is a very personalized medical intervention.”
Ideally, researchers would like to apply precision medicine to every disease, not just hemophilia or cancer. “The goal is to use precision medicine for every patient who walks in the door,” Dr. Rao said. It all comes down to identifying and understanding the mechanisms behind each disease so that physicians can prescribe treatments that are more effective. This research will take time, but with its critical mass of experts, Versiti Blood Research Institute is poised to make a big impact.
About the experts:
Weiguo Cui, MD, PhD, is an investigator at Versiti Blood Research Institute and an associate professor in the Department of Microbiology and Immunology at the Medical College of Wisconsin.
Lynn Malec, MD, MSc, is an associate investigator at Versiti Blood Research Institute and the medical director at Versiti Comprehensive Center for Bleeding Disorders.
Sid Rao, MD, PhD, is an associate investigator at Versiti Blood Research Institute and an associate professor in the Departments of Pediatrics and Cell Biology, Neurobiology, and Anatomy at the Medical College of Wisconsin.
Nan Zhu, PhD, is an associate investigator at Versiti Blood Research Institute.