Research Program Overview

The biology and behavior of tumors is determined by mutations. Our work has established a foundation for the first molecular genetic classification of clear cell RCC (ccRCC). We have also recently completed the first integrated genomic analysis of non-clear cell RCC. We have uncovered several genes 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 three signaling pathways - they involve, pVHL, mTORC1 and TFEB. Among other discoveries, our research has led to the identification of a critical regulator of mTORC1 and a novel effector. Read more.

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 completed a screen of 200,000 compounds and identified several promising candidates. Our next challenge is to determine which leads to focus on. Read more.

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. In addition, we recently reported the first genetically-engineered mouse model reproducing the mutations of ccRCC. Read more.

Biomarkers, indicators providing information about tumor behavior, are needed to facilitate the translation of basic research findings into the clinic. Building upon our gene discovery program, Dr. Kapur has developed several tests that can be applied to patient tumor samples in routine clinical practice that inform about the mutational state of renal tumors. We believe that these tests will likely inform patient treatment in the future. Read more.

Clinical trials are needed to evaluate promising drugs and test interesting concepts. An everolimus neoadjuvant trial evaluated an mTORC1 inhibitor before and after surgery for patients with metastatic RCC. Another trial evaluates whether responsiveness to IL2 can be increased by the addition of stereotactic radiation. A third trial seeks to evaluate the potential of a novel class of drugs, immune checkpoint inhibitors, against renal cancer. Read more.