John M. Perry, PhD
Research Faculty PhD; Assistant Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Assistant Professor of Pediatrics, University of Kansas School of Medicine
John Perry, PhD, Doctoral Research Faculty, was recently awarded a two-year, $200,000 Early Career Investigator Grant Program award from the V Foundation for Cancer Research. The grant was made possible through a partnership with the Kansas City Chiefs. Todd Bradley, PhD, is a co-investigator on the project.
Dr. Perry’s study is titled “Harnessing anti-cancer immunity to vaccinate against treatment failure and relapse.”
As Dr. Perry explained, resistance to cancer treatments remains a critical, unsolved problem.
Recent studies have found that an immunosurveillance system normally prevents the development of cancer. Pre-malignant cells must either hide from or reprogram the immune system to avoid recognition. Immunotherapy has been highly successful in a subset of adult cancers; however, immunotherapeutic solutions for pediatric cancers have been particularly limited. Typically, successful treatment continues to involve the use of highly toxic drugs, which are immunosuppressive and often cause life-long complications.
Residual leukemia stem cells (LSCs) underlie resistance but targeting them remains elusive. Consequently, relapse occurs in 20-25% of pediatric leukemia patients, with long-term survival rates ranging from only 15-50%. This situation has remained essentially unchanged for decades, indicating an urgent need to develop new therapeutic strategies focused on overcoming therapeutic resistance, Dr. Perry explained.
Two genetic pathways, termed the Wnt/beta-catenin and PI3K/Akt pathways, which are among the most frequently activated in human cancer, interact to drive LSC development and resistance to therapy, including immunotherapy.
“Unexpectedly, we found that long-used chemotherapy drugs, the anthracycline antibiotics including doxorubicin (DXR) and daunorubicin (DNR), inhibit the cooperative interaction of these pathways at low doses. Unlike current clinical practice of using DXR as a broadly toxic drug, we repurposed it to inhibit Akt:beta-catenin interaction and specifically target therapy-resistant LSCs in a mouse leukemia model,” said Dr. Perry.
Targeted DXR treatment, unlike the immunosuppressive clinical dose, reactivates anti-cancer immunosurveillance against therapy-resistant LSCs. “How it does so and thus how we might improve these responses in the clinic to avoid broadly toxic treatments is mysterious. Here, we will use single cell genomics coupled with ongoing studies to obtain a comprehensive view of immune system effects of targeted anthracycline treatment. This will ultimately inform the design of more durable cures with fewer side effects,” explained Dr. Perry.
The V Foundation for Cancer Research was founded by ESPN and legendary basketball coach Jim Valvano with one goal in mind: to achieve Victory Over Cancer®. Since its formation in 1993, the V Foundation has awarded more than $250 million in cancer research grants nationwide and has become one of the premier supporters of cutting-edge cancer research. The purpose of the V Foundation for Cancer Research Grant Program is to support cancer research and related programs that are designed to change the course of cancer.
“We support projects that improve the lives of people with cancer, research that provides critical data that enhances understanding of the causes, treatment, and cure of cancers, and training for promising individuals dedicated to cancer prevention, research, and/or patient care,” organizers wrote.
Funding for the grant comes from a variety of sources, including the University of Kansas Health System and KU Endowment.