Kidney cancer is one of the top ten most common cancers in the U.S. and is particularly prevalent in Texas. Consistent with the stated SPORE purpose, our objective is to develop a thriving infrastructure supporting state-of-the-art investigator-initiated translational research that will contribute to improved prevention, early detection, diagnosis, and treatment of kidney cancer (both adult and pediatric). At UT Southwestern Medical Center (UTSW), we believe that outstanding basic science sets the foundation for outstanding translation. UTSW investigators have made seminal discoveries in kidney cancer, including (i) the discovery of the gene encoding HIF -2? - the main driver of lear-cell renal cell carcinoma (ccRCC); (ii) the development of a highly specific first-in-class inhibitr of the HIF-2 transcription factor, traditionally considered undruggable; (iii) the identificationof mutations in the BAP1 gene in ccRCC; (iv) the establishment of the first molecular genetic classification of sporadic ccRCC; (v) the discovery of a novel familial kidney cancer syndrome; (vi) the development of novel non-invasive tools for imaging tumor metabolism in patients; and (vii) the discovery of DROSHA mutations in Wilms tumors. These and other exciting discoveries were the basis of a Kidney Cancer Program (KCP; www.utsouthwestern.edu/research/kidney-cancer/index.html) involving over 70 UTSW faculty. This SPORE contains four projects: Project 1: Targeting HIF-2 for the treatment of clear-cell renal cell carcinoma; Project 2: Evaluation of the functional and clinical significance of the novel tumor suppressor gene BAP1; Project 3: Clinically actionable biomarkers from renal cell carcinoma metabolism and imaging; and Project 4: Prognostic significance and therapeutic potential of DROSHA mutations in Wilms tumor. They are supported by an Administrative Core (Core A) and three other cores: Core B - an innovative Biospecimen and Pathology Resources Core with a live BioBank; Core C - a Data Analytics Core supporting a pioneering web-tool linking samples to clinical information and integrated genomics; and Core D - an outstanding Translational Imaging Core built around tools developed to study kidney cancer. A Developmental Research Program and a Career Enhancement Program thrive upon the wide scope of kidney cancer research at UTSW illustrated by the 19 LOIs with kidney-cancer relevant preliminary data submitted. Our Patient Advocate Program is comprised of six patient advocates including both experienced advocates as well as members of our kidney cancer community. The projects outlined illustrate how rigorous basic research using cellular, molecular, structural, biochemical, and genetic experimental approaches has increased our knowledge of kidney cancer, and is impacting the clinic. In summary, this Kidney Cancer SPORE represents a multidisciplinary effort from talented basic scientists, physician-scientists, and clinicians that synergistically leverages the strengths and resources we have developed in the Kidney Cancer Program to advance kidney cancer translational research, with the ultimate goal of improving kidney cancer patient outcomes.

Public Health Relevance

Discoveries by UTSW investigators have transformed the field of kidney cancer. The successful achievement of the project aims proposed in this SPORE application will inform the global standard of diagnosis and treatment of kidney cancer, and lead to improved care.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
1P50CA196516-01A1
Application #
9071063
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Hruszkewycz, Andrew M
Project Start
2016-08-01
Project End
2021-07-31
Budget Start
2016-08-01
Budget End
2017-07-31
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Kay, Fernando U; Canvasser, Noah E; Xi, Yin et al. (2018) Diagnostic Performance and Interreader Agreement of a Standardized MR Imaging Approach in the Prediction of Small Renal Mass Histology. Radiology 287:543-553
Chen, Xi; Zhou, Zhiguo; Hannan, Raquibul et al. (2018) Reliable gene mutation prediction in clear cell renal cell carcinoma through multi-classifier multi-objective radiogenomics model. Phys Med Biol 63:215008
Puertollano, Rosa; Ferguson, Shawn M; Brugarolas, James et al. (2018) The complex relationship between TFEB transcription factor phosphorylation and subcellular localization. EMBO J 37:
Chen, Kenneth S; Stroup, Emily K; Budhipramono, Albert et al. (2018) Mutations in microRNA processing genes in Wilms tumors derepress the IGF2 regulator PLAG1. Genes Dev 32:996-1007
O'Kelly, Devin; Zhou, Heling; Mason, Ralph P (2018) Tomographic breathing detection: a method to noninvasively assess in situ respiratory dynamics. J Biomed Opt 23:1-6
Wang, Xinzeng; Pirasteh, Ali; Brugarolas, James et al. (2018) Whole-body MRI for metastatic cancer detection using T2 -weighted imaging with fat and fluid suppression. Magn Reson Med 80:1402-1415
Courtney, Kevin D; Infante, Jeffrey R; Lam, Elaine T et al. (2018) Phase I Dose-Escalation Trial of PT2385, a First-in-Class Hypoxia-Inducible Factor-2? Antagonist in Patients With Previously Treated Advanced Clear Cell Renal Cell Carcinoma. J Clin Oncol 36:867-874
Krajewski, Katherine M; Pedrosa, Ivan (2018) Imaging Advances in the Management of Kidney Cancer. J Clin Oncol :JCO2018791236
Carbone, Michele; Amelio, Ivano; Affar, El Bachir et al. (2018) Consensus report of the 8 and 9th Weinman Symposia on Gene x Environment Interaction in carcinogenesis: novel opportunities for precision medicine. Cell Death Differ 25:1885-1904
Kay, Fernando U; Pedrosa, Ivan (2018) Imaging of Solid Renal Masses. Urol Clin North Am 45:311-330

Showing the most recent 10 out of 28 publications