We are a clinical and translational research team working on cancers of the genitourinary tract. While our group does research pertaining to several different urological cancers, we are particularly interested in bladder and prostate cancer. Our approach to research is highly disease focused, which means that we use a wide variety of research methodologies to investigate a single cancer. For example, we use animal models, genetic and immunologic examination of human bladder cancer biospecimens, and biomedical engineering to develop new tests and treatments for bladder cancer. At the same time, we lead several clinical trials in patients with bladder cancer testing new therapies and diagnostic tests. Our laboratory is therefore exceptionally positioned to translate pre-clinical research to early clinical trials. Our laboratory is an excellent training ground for budding surgeon scientists.
Key Projects and Achievements
Our laboratory is part of the Duke Cancer Institute’s multidisciplinary Genitourinary Cancer Laboratory, a dedicated team of researchers from different academic backgrounds focused on the common problem of genitourinary malignancies. We are co-located in a large, open concept, shared-resource, wet laboratory environment on the 3rd floor of the Snyderman building. We are heavily committed to team science and multidisciplinary research and encourage new collaborations with outside groups.
Tumor immunology and immunotherapy
Our research has addressed the role of several co-stimulatory molecules (a.k.a. immune checkpoints) in urologic tumors. Our team was the first to describe the role of PD-L1 in bladder cancer and provided early evidence that it might adversely affect outcomes. Dr. Inman is involved in several clinical trials using PD-L1 and PD-1 blocking antibodies for bladder cancer. In conjunction with this, the team also characterized a soluble form of PD-L1 that is biologically active and exhibits immunosuppressive effects in cancer patients. This is present in biofluids such as urine and blood. We developed a diagnostic test to measure the presence of this biomarker in body fluids. Lastly, we were part of the first team to describe the important role of B7-H3 in prostate cancer and how it too negatively affects outcomes. We are currently assessing B7-H3 as a prostate cancer biomarker (serum and exosomes) and are developing a dendritic cell vaccine that presents antigen and block B7-H3 simultaneously (Grant: DOD-CDMRP PCRP PC150161 PI: Inman BA).
Hyperthermia and heat-targeted therapy
Our team performed the first clinical trials of two novel treatments for non-invasive bladder cancer: deep regional hyperthermia and convection hyperthermia. We were awarded the best clinical paper of 2014 by the International Journal of Hyperthermia for one of these trials. The team has also developed novel devices and methods for performing bladder hyperthermia in the lab, such as magnetic nanoparticle hyperthermia and gold nanoparticle hyperthermia, and we have has created preclinical models for these therapies. Recently, we have extended our methods to include novel heat-targeted drug delivery and heat-mediated immune stimulation. We are also exploring combinations of hyperthermia and immunotherapy (Grant: DOD-CDMRP PRCRP CA160715 PI: Inman BA).
Diagnostic test development
Our team has studied several novel biomarkers for bladder cancer including urine-based diagnostic assays and tumor-based genetic sequencing classifiers. Where possible we have collaborated in multi-institutional efforts to increase generalizability. We have also carefully evaluated the performance of existing bladder cancer biomarkers and demonstrated key problems with these tests using very large sample sets.
Drug development and clinical trials
Our team has investigated and developed several novel therapies for urologic cancers. This includes performing early preclinical development and translating discoveries to human trials. In addition, Dr. Inman is overall or site PI for several clinical trials testing new drugs and immunotherapies for genitourinary cancers.
Bladder cancer genetics
Our team recently began working on the genetics of bladder cancer. Presently, we have two small grants with the North Carolina State University College of Veterinary Medicine looking at human and canine bladder cancer genetics with respect to their shared environmental causes (mutagens) and their genetic drivers of death. We also have two funded projects with a colleague at Duke Singapore (Steve Rozen) addressing the genetic evolution of bladder cancer and key environmental signatures of cancer.
We accept medical students, urology residents, and urologic oncology fellows as trainees in the laboratory.
Please contact Tracy Hatt for further information.