National Cancer Institute renews $11.5 million program of excellence award in kidney cancer
DALLAS – Sept. 19, 2022 – The National Cancer Institute (NCI) has renewed UT Southwestern’s Harold C. Simmons Comprehensive Cancer Center Kidney Cancer Program (KCP) Specialized Program of Research Excellence (SPORE) award. First awarded in 2016, the KCP SPORE is focused on translating discoveries and innovation at UT Southwestern into advances in patient care.
Kidney cancer is the eighth most common cancer and is particularly prevalent in Texas. Approximately 2% of men and 1% of women are diagnosed with kidney cancer in the U.S. during their lifetimes. While most kidney tumors are diagnosed early, up to 50% of patients develop metastases. Despite remarkable advances, metastatic kidney cancer remains largely incurable.
With the purpose of accelerating the translation of discoveries to the clinic, the NCI SPORE program funds approximately 50 programs of research excellence across cancer types. There are two SPOREs in kidney cancer nationwide: one at the Dana-Farber/Harvard Cancer Center – a consortium involving Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, and Massachusetts General Hospital – and one at UT Southwestern.
Led by James Brugarolas, M.D., Ph.D., Director of the UT Southwestern Kidney Cancer Program, and Payal Kapur, M.D., Group Leader of UT Southwestern Genitourinary Pathology and KCP Co-Leader of Pathology, the KCP SPORE encompasses three main projects and was ranked by NCI in the uppermost tier, in the “exceptional” category.
“These projects delve into the most promising therapeutic areas – immunotherapy, targeted therapy, and metabolism,” said Dr. Brugarolas. “Together, they speak to the breadth of kidney cancer research and expertise at UT Southwestern.” Expanding the reach, the SPORE provides funding for early-stage research projects and supports several enabling core facilities.
Project 1: Targeting HIF-2 in Renal Cell Carcinoma
Project 1 builds upon the success of the previous SPORE award (2016-present), which culminated in the development and eventual approval of belzutifan. Belzutifan is a first-in-class drug that inactivates HIF-2ɑ (hypoxia-inducible factor 2-alpha), arguably the most important driver of kidney cancer. HIF-2ɑ was discovered at UT Southwestern, where a vulnerability in its structure was identified and exploited by UT Southwestern researchers to develop a drug. Belzutifan was approved by the Food and Drug Administration in 2021, providing for the first time a medication for patients with familial kidney cancer. While the KCP team speculates that the drug is likely to control the disease for years, their discovery of resistance mutations spurred them to develop next-generation drugs. Project 1 investigators are collaborating with Arrowhead Pharmaceuticals in the development of an RNA-based HIF-2ɑ inhibitor. “No RNA drugs have shown success in oncology yet, but we are enthusiastic about this innovative approach,” said Dr. Brugarolas, Project 1 Leader. Accompanying the drug is a novel radiology test to monitor HIF-2ɑ in patients, which is being developed in collaboration with Xiankai Sun, Ph.D., Director of the Cyclotron and Radiochemistry Program, and the project Co-Leader.
Project 2: Defining Targetable Metabolic Dependencies in Human Renal Cell Carcinoma
Also a continuation of the previous SPORE, Project 2 builds upon the Metabolism Lab, an innovative platform to characterize how kidney tumors are nourished, identify nutrient dependencies, and develop metabolism-targeting drugs. The approach builds upon an unprecedented characterization of kidney cancer metabolism using labeled nutrients infused in patients, and the development of faithful laboratory models, including possibly the largest patient tumor transplant program into mice. The project is led by Ralph DeBerardinis, M.D., Ph.D., KCP Co-Leader of Metabolism, and Kevin Courtney, M.D., Ph.D.
Project 3: Maximizing Anti-Tumor Activity through Simultaneous Activation of the Innate and Adaptive Immune System in Kidney Cancer
Project 3 builds upon Breakthrough Prize discoveries by Zhijian (James) Chen, Ph.D., leading to the development of a new immunotherapy (IMSA101) now in clinical trials. IMSA101 activates STING, a master regulator of the so-called “innate” arm of the immune system. IMSA101 will be combined with radiation and an immune checkpoint inhibitor to simultaneously activate the two arms of the immune system. Leading this project are Raquib Hannan, M.D., Ph.D., Zhijian (James) Chen, Ph.D., and Hans Hammers, M.D., Ph.D.
Along with the main projects, the KCP SPORE will continue to promote kidney cancer research through the Development Research and Career Enhancement Programs (DRP and CEP, respectively). These programs already funded 35 projects at UT Southwestern during the first award period.
“The CEP and DRP are enabling mechanisms to venture in new directions, invite new investigators into the field, and diversify our workforce,” said Maralice Conacci-Sorrell, Ph.D., a Co-Director, along with Qing Zhang, Ph.D., and Denise Marciano, M.D., Ph.D.
“Aided by the SPORE, the KCP has become one of the largest, if not the largest, kidney cancer program in the country,” said Dr. Kapur.
Supporting the research are four Core Facilities. An Administrative Core coordinates activities of the SPORE. Led by Dr. Kapur, a Pathology Core provides expert pathological support and samples for research. An Imaging Core is led by Ivan Pedrosa, M.D., Ph.D., Vice Chair of Radiology Research and Co-Leader of the KCP, as well as Dr. Sun, and delivers innovative approaches to characterize kidney cancer. Finally, the Data Analytics Core, which is led by Chul Ahn, Ph.D., Director of Biostatistics at Simmons Cancer Center, and Alana Christie, M.S., Co-Leader for Data Analytics of the KCP, assists with data management and statistics.
“The SPORE brings together an exceptional team of investigators across different areas driving advances in patient care,” said Dr. Brugarolas. Complementing the research are passionate advocates. “We are indebted to our advocates, and in particular our patient advocates, who have been at the core of our program since its inception,” he added.
“Discoveries by the SPORE team have been paradigm setting and practice changing,” said Carlos L. Arteaga, M.D., Director of the Simmons Comprehensive Cancer Center. “With this renewal, some of the most urgent questions in kidney cancer will be addressed,” he added. “We appreciate the National Cancer Institute support of this engine of discovery, innovation, and translation to advance patient care.”
UT Southwestern is home to one other SPORE in lung cancer, a collaborative program with MD Anderson Cancer Center which represents the longest continuously funded SPORE program, led by John Minna, M.D.
Dr. Arteaga holds the Lisa K. Simmons Distinguished Chair in Comprehensive Oncology. Dr. Brugarolas holds the Sherry Wigley Crow Cancer Research Endowed Chair in Honor of Robert Lewis Kirby, M.D. Dr. Chen holds the George L. MacGregor Distinguished Chair in Biomedical Science. Dr. Conacci-Sorrell holds the John P. Perkins Distinguished Professorship in Biomedical Science and is a Virginia Murchison Linthicum Scholar in Medical Research. Dr. DeBerardinis holds the Joel B. Steinberg, M.D., Distinguished Chair in Pediatrics and is a Sowell Family Scholar in Medical Research. Dr. Hammers is a Eugene P. Frenkel, M.D. Scholar in Clinical Medicine. Dr. Marciano holds the Carolyn R. Bacon Distinguished Professorship in Medical Science and Education. Dr. Minna holds the Max L. Thomas Distinguished Chair in Molecular Pulmonary Oncology and the Sarah M. and Charles E. Seay Distinguished Chair in Cancer Research. Dr. Pedrosa holds the Jack Reynolds, M.D., Chair in Radiology. Dr. Sun holds the Dr. Jack Krohmer Professorship in Radiation Physics.
UT Southwestern and some of its researchers will receive financial compensation through prior agreements with Peloton Therapeutics based on belzutifan’s FDA approval and sales.
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 26 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 100,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits a year.