University of Texas Southwestern Medical Center SPORE in Kidney Cancer

德克萨斯大学西南医学中心 SPORE 在肾癌中的应用

• 批准号: 10706530
• 负责人: James Brugarolas
• 金额: $ 217.34万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10706530
• 关键词: Accounting; Address; Angiogenesis Inhibitors; Antigen Presentation; Area; Bioinformatics; Biological Markers; Biotechnology; Bypass; Carbon; Cell Proliferation; Cell Survival; Cessation of life; Chemicals; Citric Acid Cycle; Clear Cell; Clear cell renal cell carcinoma; Collaborations; Comprehensive Cancer Center; Computerized Medical Record; Core Facility; Data Analytics; Dependence; Development; Diagnosis; Disease; Drug Screening; Education; Enzymes; Evaluation; Failure; Foundations; Funding; Generations; Genes; Genomics; Germ-Line Mutation; Glutaminase; Glutamine; Glycogen; Growth; Heart failure; Hypertension; Image; Immune checkpoint inhibitor; Immune system; Immunotherapy; In complete remission; Individual; Inflammation; Infusion procedures; Innate Immune System; International; Isotope Labeling; KDR gene; Link; Lipids; Medical; Medical center; Metabolic; Metabolism; Modeling; Nitrogen; Nivolumab; Nutrient; Pathology; Pathway interactions; Patient Care; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Phenotype; Phosphotransferases; Physiological; Prize; Process; Production; Proteinuria; Radiation; Recording of previous events; Renal Cell Carcinoma; Renal carcinoma; Research; Research Personnel; Resistance; STING agonists; Sagittaria; Small Interfering RNA; Structure; Survival Rate; Technology; Texas; Therapeutic; Toxic effect; Tracer; Translating; Translations; Tumor Bank; Tumor Promotion; Tyrosine Kinase Inhibitor; Universities; Update; VHL mutation; Vascular Endothelial Growth Factors; angiogenesis; anticancer research; arm; career; clinical practice; data management; immunogenic; in vivo; inhibitor; innovation; mortality; mutant; novel therapeutic intervention; novel therapeutics; palliative; patient population; phase I trial; predictive marker; programs; radiotracer; real time monitoring; resistance mutation; safety and feasibility; side effect; stemness; success; targeted treatment; tool; transcription factor; tumor; tumorigenesis

Overall Summary Particularly prevalent in Texas, renal cell carcinoma (RCC) is lethal when metastatic. To address this unmet medical need, the UTSW Kidney Cancer SPORE has developed a comprehensive therapeutic program in proven (targeted therapies and immunotherapy) and innovative (metabolism-directed) areas. Arguably, the most important driver of RCC is HIF2α. Discovered at UTSW, and regarded as undruggable, structural studies revealed a vulnerability that was exploited through a chemical screen leading to the founding of Peloton Therapeutics in the UTSW BioCenter and the development of PT2385 and PT2977. During the previous funding period, Project 1 investigators validated HIF2α as a target, identified putative biomarkers of dependency, executed a phase 1 trial, identified resistance mutations, and established HIF2α as a core dependency. Culminating the vertical collaboration and program success, Peloton was acquired by Merck, and PT2977 (also called belzutifan) gained FDA approval. During the next period, an innovative siRNA-based, second-generation inhibitor targeting both wild-type and resistant mutant HIF2α will be co-developed together with a ground- breaking imaging radiotracer enabling HIF2α evaluation in patients. Project 2 investigators exploit a profound link between RCC and metabolism. Using pioneering isotope-labeled nutrient infusions, Project 3 investigators established during years 1-5 that glutamine is a key nutrient fueling RCC growth in patients. In years 7-12, they will deploy the authenticated In Vivo Metabolism Lab to target glutamine bypass pathways, likely explaining the recent failure of glutaminase inhibitors. Finally, by leveraging Breakthrough Prize-recognized research at UTSW leading to a new innate immune system-activating drug, Project 3 investigators propose a paradigm shift in immunotherapy development involving the coordinated activation of the adaptive and innate arms (as it occurs physiologically). Together with previously commended development and career-enhancing programs, SPORE investigators are supported by four Cores. A forward-looking Administrative Core (Core A) serves as a hub. A Pathology Core (Core B) brings to bear one of the largest and most sophisticated RCC tumor banks and expertise supporting national efforts. A Data Analytics Core (Core C) assists with statistical support, bioinformatics, and data management with an avant-garde tool that automatically extracts information from the electronic medical record, self-updates, and links this information to experimental genomics and the tumor bank. An Imaging Core (Core D) delivers enabling technologies, including IND-holding innovative tracers, and unqualified expertise. Building upon the Simmons Comprehensive Cancer Center Kidney Cancer Program and its history of collaborative, interdisciplinary cancer research, SPORE Projects and Cores provide an engine of discovery, innovation, and translation supporting national and international efforts to advance patient care, research, and education.

整体总结

项目成果

Quantitative Methods in Abdominal MRI: Perfusion Imaging.

• DOI: 10.1097/rmr.0000000000000145
• 发表时间: 2017-12
• 期刊: Topics in magnetic resonance imaging : TMRI
• 作者: Madhuranthakam AJ;Yuan Q;Pedrosa I
• 通讯作者: Pedrosa I

Stereotactic Ablative Radiation for Systemic Therapy-naïve Oligometastatic Kidney Cancer.

• DOI: 10.1016/j.euo.2022.06.008
• 发表时间: 2022-12
• 期刊: EUROPEAN UROLOGY ONCOLOGY
• 影响因子: 8.2
• 作者: Hannan, Raquibul;Christensen, Michael;Christie, Alana;Garant, Aurelie;Pedrosa, Ivan;Robles, Liliana;Mannala, Samantha;Wang, Chiachien;Hammers, Hans;Arafat, Waddah;Courtney, Kevin;Bowman, Isaac A.;Sher, David;Ahn, Chul;Cole, Suzanne;Choy, Hak;Timmerman, Robert;Brugarolas, James
• 通讯作者: Brugarolas, James

HIF2 Inactivation and Tumor Suppression with a Tumor-Directed RNA-Silencing Drug in Mice and Humans.

• DOI: 10.1158/1078-0432.ccr-22-0963
• 发表时间: 2022-12-15
• 期刊: CLINICAL CANCER RESEARCH
• 影响因子: 11.5
• 作者: Ma, Yuanqing;Joyce, Allison;Brandenburg, Olivia;Saatchi, Faeze;Stevens, Christina;Tcheuyap, Vanina Toffessi;Christie, Alana;Do, Quyen N.;Fatunde, Oluwatomilade;Macchiaroli, Alyssa;Wong, So C.;Woolford, Layton;Yousuf, Qurratulain;Miyata, Jeffrey;Carrillo, Deyssy;Onabolu, Oreoluwa;McKenzie, Tiffani;Mishra, Akhilesh;Hardy, Tanner;He, Wei;Li, Daniel;Ivanishev, Alexander;Zhang, Qing;Pedrosa, Ivan;Kapur, Payal;Schluep, Thomas;Kanner, Steven B.;Hamilton, James;Brugarolas, James
• 通讯作者: Brugarolas, James

Magnetic Resonance Imaging Radiomics Analyses for Prediction of High-Grade Histology and Necrosis in Clear Cell Renal Cell Carcinoma: Preliminary Experience.

磁共振成像放射分析分析用于预测清晰细胞肾细胞癌中高级组织学和坏死的预测：初步经验。

• DOI: 10.1016/j.clgc.2020.05.011
• 发表时间: 2021-03
• 期刊: Clinical genitourinary cancer
• 影响因子: 3.2
• 作者: Dwivedi DK;Xi Y;Kapur P;Madhuranthakam AJ;Lewis MA;Udayakumar D;Rasmussen R;Yuan Q;Bagrodia A;Margulis V;Fulkerson M;Brugarolas J;Cadeddu JA;Pedrosa I
• 通讯作者: Pedrosa I

What morphology can teach us about renal cell carcinoma clonal evolution.

哪些形态学可以告诉我们肾细胞癌克隆进化。

• 发表时间: 2020
• 期刊: Kidney cancer journal : official journal of the Kidney Cancer Association
• 作者: Kapur,Payal;Christie,Alana;Rajaram,Satwik;Brugarolas,James
• 通讯作者: Brugarolas,James