DALLAS – September 19, 2022 – The National Cancer Institute (NCI) has renewed the Harold C. Simmons Comprehensive Cancer Center’s Honors Program for Research Excellence (SPORE) award from the Harold C. Simmons Comprehensive Cancer Program (KCP). First awarded in 2016, the KCP SPORE focuses on translating discoveries and innovation at UT Southwestern into advances in patient care.
Kidney cancer is the eighth most common cancer and is especially prevalent in Texas. In the United States, approximately 2% of men and 1% of women are diagnosed with kidney cancer during their lifetime. While most kidney tumors are diagnosed early, up to 50% of patients develop metastases. Despite remarkable progress, metastatic kidney cancer remains largely incurable.
James Brugarolas, MD, Ph.D.
In an effort to accelerate the translation of discoveries into the clinic, the NCI SPORE program funds approximately 50 research excellence programs in all types of cancer. There are two kidney cancer SPOREs nationwide: one at the Dana-Farber/Harvard Cancer Center—a consortium involving the Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, and Massachusetts General Hospital—and the other at UT Southwestern.
Led by James Brugarolas, MD, Ph.D., UT Southwest Kidney Cancer Program Director, and Payal Kapur, MD, UT Southwest Genitourinary Pathology Group Leader UT and co-lead of KCP pathology, the KCP SPORE encompasses three main projects and has been rated by the NCI at the highest level, in the category of “outstanding”.
“These projects explore the most promising therapeutic areas – immunotherapy, targeted therapy and metabolism,” said Dr Brugarolas. “Together they are testament to the breadth of kidney cancer research and expertise at UT Southwestern.” Broadening the scope, SPORE provides funding for early-stage research projects and supports several enabling base facilities.
Project 1: Targeting HIF-2 in renal cell carcinoma
Project 1 builds on the success of the previous SPORE award (2016-present), which resulted 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 factor in 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 a drug for patients with familial kidney cancer for the first time. While the KCP team speculates that the drug is likely to control the disease for years, their discovery of resistance mutations prompted them to develop next-generation drugs. Project 1 researchers are collaborating with Arrowhead Pharmaceuticals to develop an RNA-based HIF-2ɑ inhibitor. “No RNA-based drug has been proven in oncology yet, but we are excited about this innovative approach,” said Dr. Brugarolas, project leader 1. The drug comes with a new 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 co-lead of the project.
Project 2: Defining targetable metabolic dependencies in human renal cell carcinoma
Also following on from the previous SPORE, Project 2 builds on the Metabolism Lab, an innovative platform to characterize how kidney tumors are nourished, identify nutritional dependencies and develop drugs targeting metabolism. The approach builds on an unprecedented characterization of kidney cancer metabolism using labeled nutrients infused into patients, and the development of faithful laboratory models, including perhaps the largest transplant program patient tumors in mice. The project is led by Ralph DeBerardinis, MD, Ph.D., co-lead of the Metabolism KCP, and Kevin Courtney, MD, Ph.D.
Project 3: Maximizing anti-tumor activity by simultaneous activation of the innate and adaptive immune system in kidney cancer
Project 3 builds on the Breakthrough Prize discoveries of Zhijian (James) Chen, Ph.D., leading to the development of a novel immunotherapy (IMSA101) currently in clinical trial. 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 activate both arms of the immune system simultaneously. This project is led by Raquib Hannan, MD, Ph.D., Zhijian (James) Chen, Ph.D., and Hans Hammers, MD, Ph.D.
Along with core projects, the KCP SPORE will continue to promote kidney cancer research through the Developmental Research and Career Enhancement Programs (DRP and CEP, respectively). These programs have already funded 35 projects at UT Southwestern in the first award period.
“CEP and DRP allow mechanisms to venture in new directions, invite new researchers into the field, and diversify our workforce,” said Maralice Conacci-Sorrell, Ph.D., co-director, with Qing Zhang, Ph.D., and Denise Marciano, MD, Ph.D.
Payal Kapur, MD
“Aided by SPORE, KCP has become one of the largest, if not the largest, kidney cancer program in the country,” said Dr. Kapur.
Four main facilities support the research. An administrative core coordinates the activities of the SPORE. Led by Dr. Kapur, a Pathology Core provides expert pathology support and specimens for research. An Imaging Core is led by Ivan Pedrosa, MD, Ph.D., Vice President of Radiology Research and Co-Director of KCP, along with Dr. Sun, and offers innovative approaches to characterizing 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, MS, co-lead of KCP data analytics, helps manage data and statistics.
“SPORE brings together an exceptional team of researchers in different fields who are advancing patient care,” said Dr. Brugarolas. Passionate advocates complete the search. “We are indebted to our advocates, and in particular our patient advocates, who have been at the heart of our program since its inception,” he added.
“The SPORE team’s findings have shifted the paradigm and changed practice,” said Carlos L. Arteaga, MD, director of the Simmons Comprehensive Cancer Center. “With this renewal, some of the most pressing issues in kidney cancer will be addressed,” he added. “We appreciate the National Cancer Institute’s support of this engine of discovery, innovation and translation to advance patient care.”
UT Southwestern is home to another SPORE in lung cancer, a collaborative program with MD Anderson Cancer Center that represents the longest continuously funded SPORE program, led by John Minna, MD
Dr. Arteaga holds the Lisa K. Simmons Distinguished Chair in Global Oncology. Dr. Brugarolas holds the Sherry Wigley Crow Endowed Chair in Cancer Research in honor of Robert Lewis Kirby, MD Dr. Chen holds the George L. MacGregor Distinguished Chair in Biomedical Sciences. Dr. Conacci-Sorrell holds the John P. Perkins Professor Emeritus Chair in Biomedical Sciences and is a Virginia Murchison Linthicum Fellow in Medical Research. Dr. DeBerardinis holds the Joel B. Steinberg, MD, Distinguished Chair in Pediatrics and is a Sowell Family Scholar in Medical Research. Dr. Hammers is Eugene P. Frenkel, MD Scholar in Clinical Medicine. Dr. Marciano holds the Carolyn R. Bacon Professor Emeritus Chair in Medical Sciences 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, MD, Chair in Radiology. Dr. Sun holds the Dr. Jack Krohmer Chair in Radiation Physics.
UT Southwestern and some of its researchers will receive financial compensation through prior agreements with Peloton Therapeutics based on FDA approval and sales of belzutifan.
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s leading 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 researchers from the Howard Hughes Medical Institute. Full-time faculty of more than 2,900 are responsible for groundbreaking medical advances and committed to rapidly translating scientific research into new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 100,000 inpatients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits annually.
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