As part of the Beau Biden Cancer Moonshot initiative, the National Cancer Institute has awarded $6.3 million dollars to Dr. Nicholas Mitsiades and a multidisciplinary, collaborative team at Baylor College of Medicine to establish a Minority Patient-derived xenograft Development and Trial Center (M-PDTC). The Center will be dedicated to creating new tools that will help researchers to better understand the biological causes behind racial and ethnic health disparities in prostate and breast cancers.
Prostate cancer is the second-leading cause of cancer death in American men, behind lung cancer, taking the lives of 29,430 men annually. Mortality from prostate cancer is estimated to be about 2.5 times higher in African-American men than in Caucasian American men, making it the largest cancer disparity in the U.S., but little is known about the underlying molecular basis for the highly aggressive behavior of prostate cancer in African-American men. Now, Mitsiades, associate professor of medicine-hematology and oncology and of molecular and cellular biology at Baylor, and his team hope to change that.
The newly formed M-PDTC will bring together experts in patient-derived xenograft (PDX) model generation, molecular biology and signaling pathways, animal drug treatment studies, pathology and clinical management of prostate and breast cancer from Baylor and MD Anderson Cancer Center. The Center will be directed by Mitsiades, who also serves as associate director of the Center for the Biology of Health Disparities and is co-leader of Nuclear Receptor Program in the Dan L Duncan Comprehensive Cancer Center at Baylor. Research efforts of the M-PDTC will be co-led by prominent leaders in cancer biology at Baylor, including Drs. Bert O’Malley, Matthew Ellis, Michael Ittmann and Susan Hilsenbeck, as well as Nora Navone with MD Anderson Cancer Center.
Prostate cancer researchers at Baylor have long been leaders in health disparities research in this area. Ittmann, the William D. Tigertt Professor of Pathology at Baylor, has led several Department of Defense PCRP-funded research efforts in this area and will serve as the PDX core leader for the M-PDTC. In addition, a Baylor team led by Ittmann and Dr. Jeffrey Jones was recently awarded a Challenge Grant from the Prostate Cancer Foundation (PCF) to understand the biology of prostate cancer in African-American veterans and to elucidate the effects of exposure to battlefield chemicals such as Agent Orange on the development and progression of prostate cancer.
Dr. Salma Kaochar, assistant professor of medicine, who is spearheading Baylor efforts in prostate PDX generation for the M-PDTC, was named a 2018 PCF VAlor Young Investigator and is working on deciphering the epigenetic landscape of African-American prostate cancer in collaboration with Mitsiades and Ittmann. Baylor also is a major participant and the only participating Texas institution in the Research on Prostate Cancer in Men of African Ancestry: Defining the Roles of Genetics, Tumor Markers, and Social Stress, also known as RESPOND, a $26.5-million, multi-institutional study funded by the National Cancer Institute, the National Institute on Minority Health and Health Disparities and the Prostate Cancer Foundation. Leading the study for Baylor is Dr. Melissa Bondy, professor of medicine – epidemiology and population sciences and associate director of cancer prevention and population sciences in the Dan L Duncan Comprehensive Cancer Center at Baylor.
Mitsiades credits this existing collaborative research network and infrastructure for ideally positioning Baylor to be selected by the NCI as one of only two M-PDTCs in the country. Another important factor is that the faculty at Baylor are responsible for clinical care at two major teaching hospitals, Ben Taub Hospital and the Michael E. DeBakey Veterans Affairs Medical Center, which serve large minority populations in Houston, one of the most diverse large cities in the U.S.
“While socioeconomic and environmental factors definitely contribute to racial and ethnic cancer health disparities, there is also evidence for biological differences, and Baylor is a leader in their study,” explains Mitsiades. “Baylor faculty serves a large minority patient population in the Houston area. Together, we will establish and fully characterize ethnically diverse cancer models that will allow us to extend our precision oncology initiatives to underserved minorities in the U.S. and address these health disparities.
Baylor has been a longtime leader in the PDX generation field. In 2017, Dr. Michael Lewis, professor in the Lester and Sue Smith Breast Center at Baylor, along with Drs. Bryan and Alana Welm of the University of Utah, was awarded a multimillion dollar grant by the NCI to establish a PDX Development and Trial Center for Breast Cancer. With the funding of the M-PDTC, Baylor will now significantly expand on its capabilities in this area. Both Baylor-led Centers are part of the NCI-PDXNet, an NCI program established to coordinate collaborative, large-scale development and pre-clinical testing of targeted therapeutic agents in patient-derived models to advance the vision of cancer precision medicine.