SPORE Grant at a Glance
Awarded: August 1, 2016
Amount: $11 million
Kidney cancer continues to be a significant problem for adults and children. There are an estimated 400,000 people in the U.S. living with kidney cancer and many more worldwide. Over 60,000 new cases of kidney cancer are expected in the U.S. in 2016. Kidney cancer is one of the 10 most common tumor types in men and women and, for reasons that are poorly understood, is particularly prevalent in Texas. Despite remarkable advances leading to the approval by the FDA of multiple treatments since 2005, metastatic kidney cancer remains largely incurable. In children, kidney cancer (Wilms tumor) is curable in the majority of patients, but the treatment involves chemotherapy and often leaves lifelong debilitating effects.
The UTSW kidney cancer SPORE, one of two SPORE awards for kidney cancer in the U.S., leverages discoveries and technological innovation at UTSW to improve the treatment and diagnosis of kidney cancer.
Our SPORE team brings together an exceptional group of investigators spanning the spectrum from basic research to the clinic. The program is supported by state-of-the-art shared facilities, a remarkable scientific advisory committee, and a terrific patient advocacy group.
James Brugarolas, M.D., Ph.D.
Project 1: Evaluation of a promising new drug to treat kidney cancer
Project 1 evaluates a novel drug that blocks, arguably, the main driver of kidney cancer, the HIF-2α protein. HIF-2α was originally discovered at UTSW. Atomic studies, also performed at UTSW, found a vulnerability in the HIF-2α structure. Chemicals were identified that exploited this vulnerability. They were licensed to Peloton Therapeutics Inc., a company founded by UTSW scientists, which developed a drug (PT2385) now in clinical trials. PT2385 is a highly potent HIF-2α inhibitor that blocks the progression of kidney cancer and is well tolerated. We seek to identify patients most likely to respond to this drug, and anticipate ways in which the tumor may evade drug effects. Watch video.
Project 2: Identification of new subtypes of kidney cancer
Discoveries at UTSW using next-generation sequencing led to the identification of a gene, BAP1, that is frequently mutated in kidney cancer. Subsequent studies, also performed at UTSW, showed that BAP1 loss is an important event in kidney cancer development. Furthermore, BAP1-deficient tumors are particularly aggressive and associated with poor prognosis. This project aims to understand how BAP1 inactivation causes kidney cancer and seeks to identify vulnerabilities that can lead to new treatments.
Project 3: Applying new technologies to determine the malignant potential of small kidney tumors
The majority of small kidney tumors tend to grow slowly and may never impact patients’ health. However, some tumors can be deadly and our ability to recognize them is poor. Project 3 evaluates an innovative platform developed at UTSW to identify aggressive tumors. The methodology exploits the observation that aggressive tumors have higher needs for nutrients to sustain their growth. Understanding how nutrients are used by aggressive tumors may, in addition, expose weaknesses that can be targeted with novel approaches. Watch video.
Project 4: Investigating a new subtype of childhood kidney cancer
Using next-generation sequencing technologies, UTSW investigators discovered a new subtype of childhood kidney cancer characterized by mutations in the DROSHA gene. Project 4 focuses on understanding how these mutations turn a normal kidney cell into a tumor cell and the identification of new, less toxic treatments.
Developmental Research Program
This program provides seed funds to support innovative, high-impact, translational kidney cancer research projects.
Career Enhancement Program
This program provides seed funding to nurture talented new investigators that may become the next generation of kidney cancer researchers.
Core A: Administration
This is the organizing hub of the SPORE, providing both administrative support and scientific oversight. The administration works together with an outstanding External Advisory Board and a Patient Council.
Core B: Leveraging Biospecimen and Pathology Resources for Discovery and Innovation
This service coordinates the distribution of cancer specimens donated by patients. The facility characterizes these specimens through genomic and other analyses and generates reagents that can be used to probe kidney cancer biology. For instance, kidney cancer samples from patients are transplanted into the kidney of mice, where they grow to form human cancer in mice.
Core C: Data Analytics Support
This facility offers a centralized research design and data analysis platform that brings together the required expertise in biostatistics, bioinformatics, clinical trials, and data management for the SPORE investigators. A centerpiece is Kidney Cancer Explorer, an online database that links cancer specimens to clinical and genomic information.
Core D: Imaging Innovations in Translational Research
This Core provides imaging (radiology) services for the evaluation of kidney cancer in patients and animal models. It supports a web-based centralized archive for all projects.
Patient Advocacy Program
Patient advocates provide a patient-focused perspective to the SPORE investigators and projects.
Debbie Harvey, a senior administrator, provides much-valued administrative assistance that supports the whole SPORE program.