b'Closing Notes & TimelineFrom the Kidney Cancer Program Director TimelineThis year, more than 73,000 people will join theThe success and prestige of2003 2010 Dr. Brugarolas team reports the identification of nearly half-a-million individuals currently livingUT Southwesterns KidneyDrs. Bruick and Gardner report the structuralDr. Brugarolas reports on the potential utility ofBAP1 mutations in ccRCC. (Pea-Llopis et al., with a diagnosis of kidney cancer in the U.S.Cancer Program did notbasis for HIF heterodimerization. (Erbel et al.,mTORC1 inhibitors for an orphan disease, epithe- Nat Genet, 2012)Thats 200 new battles every day; 200 lives for- happen overnight. CurrentPNAS, 2003) lioid angiomyolipoma. (Wolff et al., J Clin Oncol,Dr. Cadeddu reports on the long-term results of ever changed.renal tumor ablation and shows that results are Since the founding of the Kidney Cancerbreakthroughs have been the2010) comparable to partial nephrectomy. (Best et al., Program in 2013, the treatment of this diseaseresult of hard work decades2011 J Urol, 2012)entered a new era at UT Southwestern Medicalin the making.Dr. Pedrosa is recruited to UT SouthwesternDrs. Kapur and Brugarolas report the devel-Center, where clinicians work together to providefrom the Beth Israel Deaconess/Harvard Canceropment of possibly the largest kidney cancer the most technically advanced surgery, radia- Center.tumorgraft platform, which will become a corner-tion, and oncology treatment options with compassionate care. These samestone of the SPORE. (Sivanand et al., Sci Transl specialists partner with scientists focused on unraveling the biology of kidney1980 After completing his radiation oncology residencyMed, 2012)cancer. Through these partnerships and discoveries, the Kidney CancerDr. Bruick, who discovered at Albert Einstein College of Medicine, Dr. Hannan Program is fueling breakthroughs.Urological Surgeon Dr. Sagalowsky joins thethe HIF-2 inhibitor. joins the faculty at UT Southwestern. 2013And the results are telling. Our survival rates are better than the nationalUrology faculty of UT Southwestern.averages, most notably for stage 4 cancer, where our five-year survival ratesDr. Garcia reports the generation of HIF-2 defi- Dr. Pedrosa becomes a member of the RenalDr. Yan reports that TREX acts as a regulator of are triple the national benchmark. A shared vision for excellence underlies the1997 cient mice. (Scortegagna et al., Nat Genet, 2003) Task Force of the Genitourinary Cancer Steeringlysosomal biogenesis and has a role in inter-success of the Kidney Cancer Program, along with an overarching commit- Drs. McKnight and Russell discover HIF-2Committee of the National Cancer Institute. feron-independent activation of antiviral genes. ment to our patients, who are the raison dtre for everything we do. It is their(hypoxia-inducible factor 2, which they nameDr. Pan reports that mTOR regulation by the TSCDr. Brugarolas group reports the identification of(Hasan et al., Nat Immunol, 2013)passion for life, courage, and resilience that inspires our program.EPAS1), arguably the most important driver ofproteins involves RHEB. (Zhang et al., Nat Cellmutations in TSC1 in ccRCC and their potentialDr. Zhijian James Chen reports the identifica-Seven years ago, we were the new kid on the block, compared to simi- kidney cancer. (Tian et al., Genes Dev, 1997) Biol, 2003) value in predicting responsiveness to drugstion of cGAS as an innate immune sensor. (Gao lar programs at our peer institutions. But because of our relative youth and2006 blocking mTOR such as temsirolimus. (Kucejovaet al., Science, 2013; Sun et al., Science, 2013)flexibility, we developed a culture of collaboration and teamwork, drawing1998 et al., Mol Cancer Res, 2011)on the strengths of the most creative thinkers within UT Southwestern andDr. Brugarolas is recruited from the Dana-FarberDrs. Bruick and Gardner report the results of a beyond. In striving for our own definition of greatness, weve become a placeDr. Beutler reports the discovery of the LPSCancer Institute/Harvard Cancer Center toDr. Brugarolas group reports the identification ofhigh-throughput screen of the UT Southwestern of enterprising agility. The kind of place that is pioneering genetic discoveries,receptor, TLR4, a Toll-like receptor. (Poltorak,UT Southwestern.a novel mTORC1 effector, the TFEB transcriptionchemical library leading to the identifica-breaking ground in biobanking and artificial intelligence, and developing first- Science, 1998) Dr. Kapur joins the faculty in the Pathologyfactor, which is implicated in translocation carci- tion of drug-like molecules that block HIF-2. in-class drugs. We are harnessing the strengths of UT Southwesterns Nobel1999 Department.nomas. (Pea-Llopis et al., EMBO J, 2011) (Scheuermann et al., Nat Chem Biol, 2013)Prize-winning faculty and acclaimed research facilities and combining it withDr. Lotan reports on the efficacy of ablative high- Dr. DeBerardinis et al. team up to treat the firstDr. Cadeddu is elected to the American 21st-century problem-solving skills. Arriving from Johns Hopkins, Dr. Cadeddu joinspatient with an FH-deficient RCC with a glycolyticAssociation of Genitourinary Surgeons.In the process, our work is being recognized: the Specialized Programthe Urology faculty. dose-per-fraction radiation in a preclinical modelinhibitor, 2DG. (Yamasaki et al., Nat Rev Urol,Drs. Kapur and Brugarolas report that BAP1 of Research Excellence Award in 2016 by the National Cancer Institute, a2001 of RCC. (Walsh et al., Eur Eurol, 2006) 2011) and PBRM1 define distinct subtypes of ccRCC. UT Southwestern Leaders in Clinical Excellence Program Development Award2007 Dr. Beutler, along with Jules A. Hoffman, is(Kapur et al., Lancet Oncol, 2013)in 2019, and the Innovation in Healthcare Finalist Award by D Magazine and DDr. Bruick reports the identification of a family ofDr. Cadeddu reports on the first single incisionawarded the Nobel Prize in Physiology orIn collaboration with the National Cancer Institute CEO in 2020. prolyl-4-hydroxylases that modify HIF. (Bruick and(transumbilical) laparoscopic nephrectomy in theMedicine for their discoveries on activation of theand several other institutions, a team led by The war on kidney cancer is not a single war. It is a series of heroic andMcKnight, Science, 2001) world. (Raman et al., Urology, 2007) innate immune system. Dr. Brugarolas reports a novel kidney cancer exhausting battles fought day after day, one patient at a time, and every fightDr. Cadeddu reports on the first percutaneousfamilial syndrome resulting from germline muta-is different. In the words of one of our wonderful Patient Advocates, Merlindakidney tumor (RFA) ablation in Texas. (Corwin and2009 tion in BAP1. (Farley et al., Mol Cancer Res, 2013)Chelette, We strive for our patients to feel known, understood, and cared for.Cadeddu, J Urol, 2001; Gettman et al., Urology, When patients come to us, we want them to know they have a team with2001)After a fellowship at MD Anderson Cancer Center,Dr. Brugarolas group reports that whereas muta-them every step of the way. That they are not alone. For me, helping to buildDr. Margulis joins the Urology faculty. tions in BAP1 and PBRM1 seem to antagonize and lead this award-winning program has been a privilege and an honor. 2002 Drs. Bruick and Gardner report the identifi- each other, SETD2 mutations cooperate with cation of a small molecule that inhibits HIF-2.PBRM1 mutations in ccRCC. (Pea-Llopis et al., Dr. Bruick reports the discovery of an asparaginylDr. Beutler receiving the Nobel Prize. Cancer Res, 2013)hydroxylase enzyme that regulates HIF. (Lando et(Scheuermann et al., PNAS, 2009)al., Genes Dev, 2002) Dr. Garcia reports the regulation of HIF by theDrs. Timmerman and Brugarolas introduce the Dr. Deisenhofer publishes the atomic structure ofdeacetylase sirtuin 1. (Dioum et al., Science,2012 concept of SBRT for oligoprogression in kidney James Brugarolas, M.D., Ph.D.the asparaginyl hydroxylase enzyme. (Dann et al.,2009) cancer. (Straka et al., J Clin Oncol, 2013)Director, Kidney Cancer Program PNAS, 2002) Arriving from the Dana-Farber Cancer Institute/ Mayor Rawlings inaugurates the Kidney Cancer Sherry Wigley Crow Endowed Chair in Cancer Research Dr. Sagalowsky is elected to the AmericanHarvard Cancer Center, Dr. Courtney joins theProgram. Professor, Internal Medicine/Hematology-Oncology Dr. Pan reports that the TSC proteins antagonizeAssociation of Genitourinary Surgeons. faculty of UT Southwestern in Medical Oncology.Cancer Biology, Genetics, Development and Disease mTOR signaling. (Gao et al., Nat Cell Biol, 2002)72 73'