Research Program Overview
Over 250,000 individuals worldwide are diagnosed with kidney cancer every year. The lifetime risk of kidney cancer in the US is estimated at 1.6%. Most kidney tumors are renal cell carcinomas (RCCs). At diagnosis, metastases are found in approximately 30% of patients. A similar percentage of patients will develop metastases after surgical resection of a localized tumor. In the metastatic setting, RCC remains largely incurable.
Our ultimate goal is to find a cure. We seek to understand the fundamental biology of RCC and to harness this knowledge to develop personalized treatment options for patients. We have created a platform for research translation that brings discoveries from the biology of kidney cancer into the clinic. This "bench-to-bedside" pipeline is built around 6 research themes:
- Molecular Genetics
The biology and behavior of tumors is determined by mutations. We have embarked on a project to discover the mutated genes that drive RCC development. Our work has established a foundation for the first molecular genetic classification of RCC. We have uncovered several genes implicated in the disease that could be targeted by the next generation of treatments. We are also pinpointing genes that may predict whether tumors will respond to certain drugs. Read more.
Following on the identification of genes driving RCC development, studies are conducted to understand how they work in tumor cells. Our efforts are currently focused on learning more about mTORC1, a critical signaling node commonly deregulated in RCC. Our research has led to the identification of a critical regulator of mTORC1 and a novel effector. Read more.
- Drug Identification
To link our discoveries about the biology of kidney cancer to drug development, assays are being developed to screen chemical libraries. The goal is to find chemicals that specifically kill tumor cells while sparing healthy ones. We have identified several promising candidates. Our next challenge is to determine which leads to focus on. Read more.
- Tumor Modeling
A roadblock in developing drugs for cancer treatment is the lack of suitable experimental models in which new drugs can be tested. We recently developed a tumor model in mice that accurately mimics the human disease. We are using this model to explore many aspects of RCC and to test drug candidates that emerge from our screens. Read more.
A biomarker, an indicator that physicians can measure (for example, using a blood test), provides information about tumor behavior. Building upon our gene discovery program, we have developed a test that can be applied to patient tumor samples in routine clinical practice. This test provides information on the activity of a pathway within the tumor and may inform patient treatment in the future. Read more.
- Clinical Trials
We have established a platform to conduct clinical trials and evaluate promising drugs. Presently, a clinical trial is ongoing to determine how tumors become resistant to mTORC1 inhibitors. Read more.
- Personalized Medicine
Our objective is personalized therapy, exploiting the molecular genetic and biological abnormalities in tumors to improve the care of patients. Read more.