UCLA Institute of Urologic Oncology
Bladder Cancer Research Program
The David Geffen School of Medicine at UCLA is ranked third in the U.S. in research dollars and ninth in research funding from the NIH. The UCLA Institute of Urologic Oncology has one of the largest and most diverse urologic oncology research programs in the nation.
The UCLA Institute of Urologic Oncology is committed to ongoing Bladder Cancer research in a quest to develop new treatments and cures for all bladder cancer patients, along with a commitment to educate and train the next generation of leading physician-scientists.
The UCLA IUO is conducting pioneering basic (bench) research, cutting-edge translational research (bench to bedside) and offering newly-designed clinical trials.
Current Basic Research Projects include:
- Understanding the mechanisms that distinct immune pathways use to regulate tumor growth and spread, which will be important in identifying targets for novel immune-based therapies 1.
Studying the role of a novel class of genes called microRNAs, and specifically the role of microRNA-21 in bladder cancer.
- In June 2000, completion of UCLA's bladder cancer tissue microarrays, comprising 3,128 samples involving 545 cases from 387 patients were integrated with UCLA Institutional Review Board approval to a linked bladder cancer clinicopathological database and are now being used to identify and evaluate molecular markers in bladder cancer 2.
Current Translational Research Projects include:
- A leader in molecular technology, UCLA spearheads targeted cancer therapy, developing personalized treatments based on the molecular signature of each patient’s cancer. The UCLA IUO is working on a promising new class of targeted therapy for bladder cancer 3.
- Understanding the molecular and genetic mechanisms of bladder cancer stem cells, which may be the origin of the cancer and important in resistance to therapies, in order to develop novel therapies to target this cell population 4, 5.
- Harnessing the effective treatments that are now available for patients with metastatic bladder cancer and re-imagining how they can be lifesaving for patients with earlier stage disease; as well as applying these treatments to cancer of the upper urinary tract, which behaves similar to bladder cancer but suffers from a lack of minimally-invasive yet effective treatments. We will continue to evaluate these treatments and delivery techniques in animal models to accrue enough data to support the application for a clinical trial.
- Investigating the use of a novel aqueous hydrogel polymer for the treatment of upper tract urothelial carcinoma (UTUC).
Dr. Nicolas Donin, UCLA urologic oncologist, is working with Dr. Karim Chamir, assistant professor UCLA urology, to investigate the use of a novel aqueous hydrogel polymer for the treatment of upper tract urothelial carcinoma (UTUC).
This novel agent has unique biophysical properties, in that at body temperature it exists as a viscous gel. When cooled down to zero degrees, it liquifies. This "reverse thermal gelation" means that the gel can be instilled into the upper urinary tract as a liquid, but as it makes contact with the tissues, it will rapidly warm to body temperature and gelatinize within the urinary tract. Because it is hydrophilic, the gel is slowly dissolved with the natural production of urine. This novel gel could be combined with various agents, including topical chemotherapy agents, which could be delivered to the upper urinary tract, resulting in prolonged sustained release of these agents at the site of UTUC tumors.
There are numerous unanswered questions regarding the safety and feasibility of the above treatment strategy. The UCLA Institute of Urologic Oncology has recently completed a 3-phase preclinical investigation in a porcine animal model, the goal of which was to evaluate the clinical and pathologic effects of both single and repeated instillations of this novel agent into the upper urinary tract. The results of their study demonstrated that the gel could be feasibly delivered in both single and serial doses, no obstruction of the urinary tract was evidence, and there appear to be no adverse affects on renal function or other laboratory parameters. These findings have been recently published in high-impact peer-reviewed Urology journals, and were presented to the FDA as part of development of this new technology for use in humans.
As a result of these encouraging findings, the FDA have approved a multicenter international clinical trial investigating this new technology for use in humans with UTUC. Patient accrual will begin in the coming year.
Accomplishing translational research goals requires a team-based approach with input from our urologic oncologists, medical oncologists, scientists here at UCLA, and from our collaborators at other institutions and those in biotech. We’re not only looking to improve the treatments themselves, but we’re also figuring out better ways to deliver treatment to our patients.
- Identification of some of the first monoclonal antibodies in bladder cancer and, by confirming their selective binding to bladder tumor sites, confirmation of their potential utility in the diagnosis and treatment of bladder cancer.
- Awarding of a National Cancer Institute $7 million multidisciplinary grant and cancer prevention clinical trial of green tea and an epidermal growth factor receptor (EGRr) antagonist.
- Our health service research is focused on the nexus of quality of care and trends in medical technology. The Urologic Diseases in America project, an NIH-funded research enterprise, evaluates quality, cost, and technology trends in major urologic conditions such as bladder cancer.
- In the 1980's, initiation of a clinical trial of BCG bladder irrigation for superficial bladder tumors constituted one of the early studies confirming the role of BCG in the treatment of carcinoma in situ of the bladder.
Clinical Trials for Bladder Cancer Currently Open for Enrollment
1. Zhang, H.; Chin, A. I. Role of Rip2 in Development of Tumor-Infiltrating MDSCs and Bladder Cancer Metastasis. PloS one 2014, 9, e94793.
2. Klatte, T.; Seligson, D. B.; Rao, J. Y.; Yu, H.; Martino, M. de; Garraway, I.; Wong, S. G.; Belldegrun, A. S.; Pantuck, A. J. Absent CD44v6 Expression Is an Independent Predictor of Poor Urothelial Bladder Cancer Outcome. The Journal of urology 2010, 183, 2403–8.
3. Li, D. R.; Zhang, H.; Peek, E.; Wang, S.; Du, L.; Li, G.; Chin, A. I. Synergy of Histone-Deacetylase Inhibitor AR-42 with Cisplatin in Bladder Cancer. Journal of Urology 2015, 194, 547–555.
4. Zhang, H.; Prado, K.; Zhang, K.; Peek, E.; Lee, J.; Wang, X.; Huang, J.; Li, G.; Pellegrini, M.; Chin, A. Biased Expression of the FOXP3del3 Isoform in Aggressive Bladder Cancer Mediates Differentiation and Cisplatin Chemotherapy Resistance. Clin Cancer Res 2016, Epub ahead.
5. Peek, E. M.; Li, D. R.; Zhang, H.; Kim, H. P.; Zhang, B.; Garraway, I. P.; Chin, A. I. Stromal Modulation of Bladder Cancer-Initiating Cells in a Subcutaneous Tumor Model. American journal of cancer research 2012, 2, 745–51.