A urine-based test for early detection and monitoring of bladder cancer and a plan to develop nanoparticles to deliver chemotherapy drugs to bladder tissue are among the first round of projects awarded research grants by the Johns Hopkins Greenberg Bladder Cancer Institute.
The institute, which aims to develop new clinical strategies for combating bladder cancer through intensive, collaborative and innovative research, each year awards grants of up to $50,000 to encourage young investigators, support pilot and exploratory projects that help advance the state of science and clinical practice in bladder cancer, and leverage existing resources and expertise. The grants, renewable for up to three years, are awarded in the following areas: genetic and epigenetic approaches; immunotherapy; targeted therapies; patient care, prevention and screening; and pioneering studies.
The 2014 awardees and their projects are:
• Trinity Bivalacqua, M.D., Ph.D., associate professor of urology, surgery and oncology at the Johns Hopkins University School of Medicine and director of urologic oncology at the Johns Hopkins Kimmel Cancer Center, for Nanomedicine Approaches for Improving Intravesical Delivery of Chemotherapeutic Agents
Bivalacqua and colleagues will develop nonadhesive, biodegradable nanoparticles loaded with chemotherapy and other solutions. They will compare the effectiveness of their nanoparticles with standard ways of delivering chemotherapy in a mouse model of bladder cancer. The hypothesis is that the nanoparticles will better sustain delivery of chemotherapy into bladder tissue, preventing tumor recurrence and progression.
• Charles Drake, M.D., Ph.D., associate professor of oncology, urology and immunology at the Johns Hopkins University School of Medicine, for Dissecting the Phenotype of CD4 and CD8 Tumor Infiltrating Lymphocytes in Advanced Bladder Cancer
Drake and others will catalogue the sequences of RNA – strings of chemical letters that form the “read out” of DNA and help construct proteins – from bladder cancer samples of people with advanced disease. He aims to identify new and existing molecules on the surface of lymphocytes – white blood cells that penetrate tumors and kill cancer cells – that regulate how the immune system identifies and marks cancer cells for destruction. The findings could help discover new targets for cancer immunotherapy.
• George Netto, M.D., director of surgical pathology and molecular diagnostics, and professor of pathology, oncology and urology at the Johns Hopkins University School of Medicine, for TERT-Promoter Mutations Urine Assay for Early Detection and Monitoring of Bladder Cancer
Netto’s project will continue work on a noninvasive, urine-based test to identify mutations in the “on-off switch” of a gene called telomerase reverse transcriptase (TERT), which is present in a range of bladder cancer precursor lesions. New experiments will determine how well a test for TERT mutations can detect bladder cancer in urine samples of individuals at high risk for bladder cancer, determine the utility of detecting TERT mutations among urine samples taken during follow-up of bladder cancer patients to monitor disease recurrence, and see if it is worth expanding the test to include additional genetic mutations found in bladder cancer.
• Peter H. O’Donnell, M.D., assistant professor of medicine at the University of Chicago Medicine Comprehensive Cancer Center, for Genetic Diversity of T Cell Receptors Impacting Anti-tumor Effects in Bladder Cancer
O’Donnell’s study will test the idea that as some bladder cancers progress, they acquire certain mutations that may activate and expand the number of tumor-infiltrating T lymphocytes (TILs), white blood cells found in tumors that kill cancer cells. Investigators will look for genetic changes in TILs that predict robustness of immune responses against bladder cancer to see if they contribute to better recurrence-free and overall survival.
• Armine Smith, M.D., assistant professor of urology at the Johns Hopkins University School of Medicine, for Pilot Study of TRAIL and BCG Combination Therapy in Bladder Cancer
Smith’s study will see if stimulating a protein called TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), which kick starts the process of cell death, will increase the effect of BCG (Bacillus Calmette-Guerrin), the main biological treatment for non-muscle invasive bladder cancer, in mice. Investigators also will collect tissue from patients with bladder cancer to identify levels of TRAIL receptors before and after BCG treatment and correlate them with treatment outcomes.
• Dan Theodorescu, M.D., Ph.D., professor of urology and director of the University of Colorado Cancer Center, for The Role of AGL, a Glycogen Debranching Enzyme in Bladder Cancer
Theodorescu’s research will study the role of AGL, an enzyme that suppresses bladder tumor growth. Patients with metastatic bladder cancer have lower levels of AGL. Scientists will track levels of AGL and another enzyme called HAS2 to determine their correlation with patient outcomes. The researchers will also study mice that do not express AGL to see if they are more susceptible to bladder cancer.
“We’re very excited about these projects, which potentially could lead to novel therapies for bladder cancer, or to optimizing and characterizing existing therapies and improving their efficacy,” says William B. Isaacs, Ph.D., professor of urology and oncology at the Johns Hopkins University School of Medicine.
Applications will be made available online in summer 2015 for the next round of funding, Isaacs said. The URL is http://pilotprojects.onc.jhmi.edu/.
The Johns Hopkins Greenberg Bladder Cancer Institute was established in May 2014, thanks to a $15 million gift from Baltimore-area commercial real estate developer Erwin L. Greenberg and his wife, Stephanie Cooper Greenberg, and a $30 million investment from The Johns Hopkins University.
The institute, the first of its kind in the world, is dedicated to advancing the scientific understanding of bladder cancer and improving its treatment. Its experts include multidisciplinary research teams from the Johns Hopkins Kimmel Cancer Center, as well as faculty from the Johns Hopkins University School of Medicine’s Department of Radiation Oncology and Molecular Radiation Sciences, the James Buchanan Brady Urological Institute at Johns Hopkins, and Johns Hopkins’ departments of Pathology and Surgery.