Kidney Cancer Program

The DF/HCC Kidney Cancer Program has established itself as a consistent leader within both DF/HCC and the broader kidney cancer research community contributing to basic, translational, and clinical research on the local, national, and international stage. 

The Program’s recent scientific efforts have focused on identifying meaningful biomarkers for early detection and prognosis, underlying mechanisms of disease biology, novel therapeutic targets for the various kidney cancer populations, and improved preclinical models for preliminary validation of these findings. In addition, the Program performs cutting-edge clinical trials that have identified potentially more effective treatments, as well as predictive and surrogate markers of efficacy that might help determine which patients will benefit from specific therapies. The Program has more than 30 members representing all DF/HCC institutions.

Recent Publications

  • Alesi N, Khabibullin D, Rosenthal DM, Akl EW, Cory PM, Alchoueiry M, Salem S, Daou M, Gibbons WF, Chen JA, Zhang L, Filippakis H, Graciotti L, Miceli C, Monfregola J, Vilardo C, Morroni M, Di Malta C, Napolitano G, Ballabio A, Henske EP. TFEB drives mTORC1 hyperactivation and kidney disease in Tuberous Sclerosis Complex. Nat Commun 2024; 15:406. PubMed
  • Murphy AJ, Cheng C, Williams J, Shaw TI, Pinto EM, Dieseldorff-Jones K, Brzezinski J, Renfro LA, Tornwall B, Huff V, Hong AL, Mullen EA, Crompton B, Dome JS, Fernandez CV, Geller JI, Ehrlich PF, Mulder H, Oak N, Maciezsek J, Jablonowski CM, Fleming AM, Pichavaram P, Morton CL, Easton J, Nichols KE, Clay MR, Santiago T, Zhang J, Yang J, Zambetti GP, Wang Z, Davidoff AM, Chen X. Genetic and epigenetic features of bilateral Wilms tumor predisposition in patients from the Children's Oncology Group AREN18B5-Q. Nat Commun 2023; 14:8006. PubMed
  • Nadal R, Valderrama BP, Bellmunt J. Progress in systemic therapy for advanced-stage urothelial carcinoma. Nat Rev Clin Oncol 2023. PubMed
  • Pal SK, Albiges L, Tomczak P, Suárez C, Voss MH, de Velasco G, Chahoud J, Mochalova A, Procopio G, Mahammedi H, Zengerling F, Kim C, Osawa T, Angel M, Gupta S, Khan O, Bergthold G, Liu B, Kalaitzidou M, Huseni M, Scheffold C, Powles T, Choueiri TK. Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial. Lancet 2023. PubMed
  • Choueiri TK, Powles T, Albiges L, Burotto M, Szczylik C, Zurawski B, Yanez Ruiz E, Maruzzo M, Suarez Zaizar A, Fein LE, Schutz FA, Heng DYC, Wang F, Mataveli F, Chang YL, van Kooten Losio M, Suarez C, Motzer RJ, . Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. N Engl J Med 2023; 388:1767-1778. PubMed
  • Choueiri TK, McDermott DF, Merchan J, Bauer TM, Figlin R, Heath EI, Michaelson MD, Arrowsmith E, D'Souza A, Zhao S, Roy A, Perini R, Vickery D, Tykodi SS. Belzutifan plus cabozantinib for patients with advanced clear cell renal cell carcinoma previously treated with immunotherapy: an open-label, single-arm, phase 2 study. Lancet Oncol. 2023; 24:553-562. PubMed
  • Choueiri TK, Eto M, Motzer R, De Giorgi U, Buchler T, Basappa NS, Méndez-Vidal MJ, Tjulandin S, Hoon Park S, Melichar B, Hutson T, Alemany C, McGregor B, Powles T, Grünwald V, Alekseev B, Rha SY, Kopyltsov E, Kapoor A, Alonso Gordoa T, Goh JC, Staehler M, Merchan JR, Xie R, Perini RF, Mody K, McKenzie J, Porta CG. Lenvatinib plus pembrolizumab versus sunitinib as first-line treatment of patients with advanced renal cell carcinoma (CLEAR): extended follow-up from the phase 3, randomised, open-label study. Lancet Oncol. 2023; 24:228-238. PubMed
  • Nassar AH, Abou Alaiwi S, Baca SC, Adib E, Corona RI, Seo JH, Fonseca MAS, Spisak S, El Zarif T, Tisza V, Braun DA, Du H, He M, Flaifel A, Alchoueiry M, Denize T, Matar SG, Acosta A, Shukla S, Hou Y, Steinharter J, Bouchard G, Berchuck JE, O'Connor E, Bell C, Nuzzo PV, Mary Lee GS, Signoretti S, Hirsch MS, Pomerantz M, Henske E, Gusev A, Lawrenson K, Choueiri TK, Kwiatkowski DJ, Freedman ML. Epigenomic charting and functional annotation of risk loci in renal cell carcinoma. Nat Commun 2023; 14:346. PubMed
  • Groha S, Alaiwi SA, Xu W, Naranbhai V, Nassar AH, Bakouny Z, El Zarif T, Saliby RM, Wan G, Rajeh A, Adib E, Nuzzo PV, Schmidt AL, Labaki C, Ricciuti B, Alessi JV, Braun DA, Shukla SA, Keenan TE, Van Allen E, Awad MM, Manos M, Rahma O, Zubiri L, Villani AC, Fairfax B, Hammer C, Khan Z, Reynolds K, Semenov Y, Schrag D, Kehl KL, Freedman ML, Choueiri TK, Gusev A. Germline variants associated with toxicity to immune checkpoint blockade. Nat Med 2022; 28:2584-2591. PubMed
  • Alchahin AM, Mei S, Tsea I, Hirz T, Kfoury Y, Dahl D, Wu CL, Subtelny AO, Wu S, Scadden DT, Shin JH, Saylor PJ, Sykes DB, Kharchenko PV, Baryawno N. A transcriptional metastatic signature predicts survival in clear cell renal cell carcinoma. Nat Commun 2022; 13:5747. PubMed
  • Bakouny Z, Sadagopan A, Ravi P, Metaferia NY, Li J, AbuHammad S, Tang S, Denize T, Garner ER, Gao X, Braun DA, Hirsch L, Steinharter JA, Bouchard G, Walton E, West D, Labaki C, Dudani S, Gan CL, Sethunath V, Carvalho FLF, Imamovic A, Ricker C, Vokes NI, Nyman J, Berchuck JE, Park J, Hirsch MS, Haq R, Mary Lee GS, McGregor BA, Chang SL, Feldman AS, Wu CJ, McDermott DF, Heng DYC, Signoretti S, Van Allen EM, Choueiri TK, Viswanathan SR. Integrative clinical and molecular characterization of translocation renal cell carcinoma. Cell Rep 2022; 38:110190. PubMed
  • Choueiri TK, Tomczak P, Park SH, Venugopal B, Ferguson T, Chang YH, Hajek J, Symeonides SN, Lee JL, Sarwar N, Thiery-Vuillemin A, Gross-Goupil M, Mahave M, Haas NB, Sawrycki P, Gurney H, Chevreau C, Melichar B, Kopyltsov E, Alva A, Burke JM, Doshi G, Topart D, Oudard S, Hammers H, Kitamura H, Bedke J, Perini RF, Zhang P, Imai K, Willemann-Rogerio J, Quinn DI, Powles T, . Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma. N Engl J Med 2021; 385:683-694. PubMed
  • Hirsch L, Martinez Chanza N, Farah S, Xie W, Flippot R, Braun DA, Rathi N, Thouvenin J, Collier KA, Seront E, de Velasco G, Dzimitrowicz H, Beuselinck B, Xu W, Bowman IA, Lam ET, Abuqayas B, Bilen MA, Varkaris A, Zakharia Y, Harrison MR, Mortazavi A, Barthélémy P, Agarwal N, McKay RR, Brastianos PK, Krajewski KM, Albigès L, Harshman LC, Choueiri TK. Clinical Activity and Safety of Cabozantinib for Brain Metastases in Patients With Renal Cell Carcinoma. JAMA Oncol 2021. PubMed
  • Tan KT, Kim H, Carrot-Zhang J, Zhang Y, Kim WJ, Kugener G, Wala JA, Howard TP, Chi YY, Beroukhim R, Li H, Ha G, Alper SL, Perlman EJ, Mullen EA, Hahn WC, Meyerson M, Hong AL. Haplotype-resolved germline and somatic alterations in renal medullary carcinomas. Genome Med 2021; 13:114. PubMed
  • Braun DA, Street K, Burke KP, Cookmeyer DL, Denize T, Pedersen CB, Gohil SH, Schindler N, Pomerance L, Hirsch L, Bakouny Z, Hou Y, Forman J, Huang T, Li S, Cui A, Keskin DB, Steinharter J, Bouchard G, Sun M, Pimenta EM, Xu W, Mahoney KM, McGregor BA, Hirsch MS, Chang SL, Livak KJ, McDermott DF, Shukla SA, Olsen LR, Signoretti S, Sharpe AH, Irizarry RA, Choueiri TK, Wu CJ. Progressive immune dysfunction with advancing disease stage in renal cell carcinoma. Cancer Cell 2021; 39:632-648.e8. PubMed
  • Bi K, He MX, Bakouny Z, Kanodia A, Napolitano S, Wu J, Grimaldi G, Braun DA, Cuoco MS, Mayorga A, DelloStritto L, Bouchard G, Steinharter J, Tewari AK, Vokes NI, Shannon E, Sun M, Park J, Chang SL, McGregor BA, Haq R, Denize T, Signoretti S, Guerriero JL, Vigneau S, Rozenblatt-Rosen O, Rotem A, Regev A, Choueiri TK, Van Allen EM. Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma. Cancer Cell 2021; 39:649-661.e5. PubMed
  • Choueiri TK, Bauer TM, Papadopoulos KP, Plimack ER, Merchan JR, McDermott DF, Michaelson MD, Appleman LJ, Thamake S, Perini RF, Zojwalla NJ, Jonasch E. Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med 2021; 27:802-805. PubMed
  • Abou Alaiwi S, Nassar AH, Adib E, Groha SM, Akl EW, McGregor BA, Esplin ED, Yang S, Hatchell K, Fusaro V, Nielsen S, Kwiatkowski DJ, Sonpavde GP, Pomerantz M, Garber JE, Freedman ML, Rana HQ, Gusev A, Choueiri TK. Trans-ethnic variation in germline variants of patients with renal cell carcinoma. Cell Rep 2021; 34:108926. PubMed
  • Choueiri TK, Powles T, Burotto M, Escudier B, Bourlon MT, Zurawski B, Oyervides Juárez VM, Hsieh JJ, Basso U, Shah AY, Suárez C, Hamzaj A, Goh JC, Barrios C, Richardet M, Porta C, Kowalyszyn R, Feregrino JP, Żołnierek J, Pook D, Kessler ER, Tomita Y, Mizuno R, Bedke J, Zhang J, Maurer MA, Simsek B, Ejzykowicz F, Schwab GM, Apolo AB, Motzer RJ, . Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med 2021; 384:829-841. PubMed
  • Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, Kopyltsov E, Méndez-Vidal MJ, Kozlov V, Alyasova A, Hong SH, Kapoor A, Alonso Gordoa T, Merchan JR, Winquist E, Maroto P, Goh JC, Kim M, Gurney H, Patel V, Peer A, Procopio G, Takagi T, Melichar B, Rolland F, De Giorgi U, Wong S, Bedke J, Schmidinger M, Dutcus CE, Smith AD, Dutta L, Mody K, Perini RF, Xing D, Choueiri TK, . Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med 2021. PubMed
  • Bakouny Z, Braun DA, Shukla SA, Pan W, Gao X, Hou Y, Flaifel A, Tang S, Bosma-Moody A, He MX, Vokes N, Nyman J, Xie W, Nassar AH, Abou Alaiwi S, Flippot R, Bouchard G, Steinharter JA, Nuzzo PV, Ficial M, Sant'Angelo M, Forman J, Berchuck JE, Dudani S, Bi K, Park J, Camp S, Sticco-Ivins M, Hirsch L, Baca SC, Wind-Rotolo M, Ross-Macdonald P, Sun M, Lee GM, Chang SL, Wei XX, McGregor BA, Harshman LC, Genovese G, Ellis L, Pomerantz M, Hirsch MS, Freedman ML, Atkins MB, Wu CJ, Ho TH, Linehan WM, McDermott DF, Heng DYC, Viswanathan SR, Signoretti S, Van Allen EM, Choueiri TK. Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma. Nat Commun 2021; 12:808. PubMed
  • McDermott DF, Lee JL, Ziobro M, Suarez C, Langiewicz P, Matveev VB, Wiechno P, Gafanov RA, Tomczak P, Pouliot F, Donskov F, Alekseev BY, Shin SJ, Bjarnason GA, Castellano D, Silverman RK, Perini RF, Schloss C, Atkins MB. Open-Label, Single-Arm, Phase II Study of Pembrolizumab Monotherapy as First-Line Therapy in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma. J Clin Oncol 2021. PubMed
  • Khanna P, Soh HJ, Chen CH, Saxena R, Amin S, Naughton M, Joslin PN, Moore A, Bakouny Z, O'Callaghan C, Catalano P, Signoretti S, McKay R, Choueiri TK, Bhasin M, Walther T, Bhatt RS. ACE2 abrogates tumor resistance to VEGFR inhibitors suggesting angiotensin-(1-7) as a therapy for clear cell renal cell carcinoma. Sci Transl Med 2021. PubMed
  • McKay RR, McGregor BA, Xie W, Braun DA, Wei X, Kyriakopoulos CE, Zakharia Y, Maughan BL, Rose TL, Stadler WM, McDermott DF, Harshman LC, Choueiri TK. Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE). J Clin Oncol 2020; 38:4240-4248. PubMed
  • Motzer RJ, Robbins PB, Powles T, Albiges L, Haanen JB, Larkin J, Mu XJ, Ching KA, Uemura M, Pal SK, Alekseev B, Gravis G, Campbell MT, Penkov K, Lee JL, Hariharan S, Wang X, Zhang W, Wang J, Chudnovsky A, di Pietro A, Donahue AC, Choueiri TK. Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial. Nat Med 2020. PubMed
  • Wang Y, Liu Y, Deng W, Fu F, Yan S, Yang H, Liu R, Geng J, Xu J, Wu Y, Ma J, Zhou J, Liu N, Jin Y, Xia R, Elias N, Lee RJ, Feldman AS, Blute ML, Colvin RB, Wu CL, Miao Y. Viral integration in BK polyomavirus-associated urothelial carcinoma in renal transplant recipients: multistage carcinogenesis revealed by next-generation virome capture sequencing. Oncogene 2020; 39:5734-5742. PubMed
  • Nuzzo PV, Berchuck JE, Korthauer K, Spisak S, Nassar AH, Abou Alaiwi S, Chakravarthy A, Shen SY, Bakouny Z, Boccardo F, Steinharter J, Bouchard G, Curran CR, Pan W, Baca SC, Seo JH, Lee GM, Michaelson MD, Chang SL, Waikar SS, Sonpavde G, Irizarry RA, Pomerantz M, De Carvalho DD, Choueiri TK, Freedman ML. Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes. Nat Med 2020. PubMed
  • Braun DA, Hou Y, Bakouny Z, Ficial M, Sant' Angelo M, Forman J, Ross-Macdonald P, Berger AC, Jegede OA, Elagina L, Steinharter J, Sun M, Wind-Rotolo M, Pignon JC, Cherniack AD, Lichtenstein L, Neuberg D, Catalano P, Freeman GJ, Sharpe AH, McDermott DF, Van Allen EM, Signoretti S, Wu CJ, Shukla SA, Choueiri TK. Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma. Nat Med 2020; 26:909-918. PubMed
  • Ravi P, Mantia C, Su C, Sorenson K, Elhag D, Rathi N, Bakouny Z, Agarwal N, Zakharia Y, Costello BA, McKay RR, Narayan V, Alva A, McGregor BA, Gao X, McDermott DF, Choueiri TK. Evaluation of the Safety and Efficacy of Immunotherapy Rechallenge in Patients With Renal Cell Carcinoma. JAMA Oncol 2020. PubMed
  • Choueiri TK, Heng DYC, Lee JL, Cancel M, Verheijen RB, Mellemgaard A, Ottesen LH, Frigault MM, L'Hernault A, Szijgyarto Z, Signoretti S, Albiges L. Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma: The SAVOIR Phase 3 Randomized Clinical Trial. JAMA Oncol 2020. PubMed
  • McGregor BA, McKay RR, Braun DA, Werner L, Gray K, Flaifel A, Signoretti S, Hirsch MS, Steinharter JA, Bakouny Z, Flippot R, Wei XX, Choudhury A, Kilbridge K, Freeman GJ, Van Allen EM, Harshman LC, McDermott DF, Vaishampayan U, Choueiri TK. Results of a Multicenter Phase II Study of Atezolizumab and Bevacizumab for Patients With Metastatic Renal Cell Carcinoma With Variant Histology and/or Sarcomatoid Features. J Clin Oncol 2020; 38:63-70. PubMed
  • Nicholson HE, Tariq Z, Housden BE, Jennings RB, Stransky LA, Perrimon N, Signoretti S, Kaelin WG. HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species. Sci Signal 2019. PubMed
  • Li H, Bullock K, Gurjao C, Braun D, Shukla SA, Bossé D, Lalani AA, Gopal S, Jin C, Horak C, Wind-Rotolo M, Signoretti S, McDermott DF, Freeman GJ, Van Allen EM, Schreiber SL, Stephen Hodi F, Sellers WR, Garraway LA, Clish CB, Choueiri TK, Giannakis M. Metabolomic adaptations and correlates of survival to immune checkpoint blockade. Nat Commun 2019; 10:4346. PubMed
  • Kennedy JC, Khabibullin D, Hougard T, Nijmeh J, Shi W, Henske EP. Loss of FLCN inhibits canonical WNT signaling via TFE3. Hum Mol Genet 2019. PubMed
  • Delto JC, Chang P, Hyde S, McAnally K, Crociani C, Wagner AA. Eliminating pseudoaneurysm and urine leak after robotic partial nephrectomy: results using the early unclamping technique. Urology 2019. PubMed
  • Gao X, McDermott DF, Michaelson MD. Enhancing Antitumor Immunity with Antiangiogenic Therapy: A Clinical Model in Renal Cell Carcinoma? Oncologist 2019; 24:725-727. PubMed
  • Michaelson MD, Gupta S, Agarwal N, Szmulewitz R, Powles T, Pili R, Bruce JY, Vaishampayan U, Larkin J, Rosbrook B, Wang E, Murphy D, Wang P, Lechuga MJ, Valota O, Shepard DR. A Phase Ib Study of Axitinib in Combination with Crizotinib in Patients with Metastatic Renal Cell Cancer or Other Advanced Solid Tumors. Oncologist 2019. PubMed
  • Voss MH, Bhatt RS, Vogelzang NJ, Fishman M, Alter RS, Rini BI, Beck JT, Joshi M, Hauke R, Atkins MB, Burgess E, Logan TF, Shaffer D, Parikh R, Moazzam N, Zhang X, Glasser C, Sherman ML, Plimack ER. A phase 2, randomized trial evaluating the combination of dalantercept plus axitinib in patients with advanced clear cell renal cell carcinoma. Cancer 2019. PubMed
  • Pignon JC, Jegede O, Shukla SA, Braun DA, Horak CE, Wind-Rotolo M, Ishii Y, Catalano PJ, Grosha J, Flaifel A, Novak JS, Mahoney KM, Freeman GJ, Sharpe AH, Hodi FS, Motzer RJ, Choueiri TK, Wu CJ, Atkins MB, McDermott DF, Signoretti S. irRECIST for the Evaluation of Candidate Biomarkers of Response to Nivolumab in Metastatic Clear Cell Renal Cell Carcinoma: Analysis of a Phase II Prospective Clinical Trial. Clin Cancer Res 2019; 25:2174-2184. PubMed
  • Martínez Chanzá N, Xie W, Asim Bilen M, Dzimitrowicz H, Burkart J, Geynisman DM, Balakrishnan A, Bowman IA, Jain R, Stadler W, Zakharia Y, Narayan V, Beuselinck B, McKay RR, Tripathi A, Pachynski R, Hahn AW, Hsu J, Shah SA, Lam ET, Rose TL, Mega AE, Vogelzang N, Harrison MR, Mortazavi A, Plimack ER, Vaishampayan U, Hammers H, George S, Haas N, Agarwal N, Pal SK, Srinivas S, Carneiro BA, Heng DYC, Bosse D, Choueiri TK, Harshman LC. Cabozantinib in advanced non-clear-cell renal cell carcinoma: a multicentre, retrospective, cohort study. Lancet Oncol. 2019; 20:581-590. PubMed
  • Chakraborty S, Balan M, Flynn E, Zurakowski D, Choueiri TK, Pal S. Activation of c-Met in cancer cells mediates growth-promoting signals against oxidative stress through Nrf2-HO-1. Oncogenesis 2019; 8:7. PubMed
  • Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT, Venugopal B, Kollmannsberger C, Negrier S, Uemura M, Lee JL, Vasiliev A, Miller WH, Gurney H, Schmidinger M, Larkin J, Atkins MB, Bedke J, Alekseev B, Wang J, Mariani M, Robbins PB, Chudnovsky A, Fowst C, Hariharan S, Huang B, di Pietro A, Choueiri TK. Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med 2019; 380:1103-1115. PubMed
  • Chakraborty AA, Laukka T, Myllykoski M, Ringel AE, Booker MA, Tolstorukov MY, Meng YJ, Meier SR, Jennings RB, Creech AL, Herbert ZT, McBrayer SK, Olenchock BA, Jaffe JD, Haigis MC, Beroukhim R, Signoretti S, Koivunen P, Kaelin WG. Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate. Science 2019; 363:1217-1222. PubMed
  • Hong AL, Tseng YY, Wala JA, Kim WJ, Kynnap BD, Doshi MB, Kugener G, Sandoval GJ, Howard TP, Li J, Yang X, Tillgren M, Ghandi M, Sayeed A, Deasy R, Ward A, McSteen B, Labella KM, Keskula P, Tracy A, Connor C, Clinton CM, Church AJ, Crompton BD, Janeway KA, Van Hare B, Sandak D, Gjoerup O, Bandopadhayay P, Clemons PA, Schreiber SL, Root DE, Gokhale PC, Chi SN, Mullen EA, Roberts CW, Kadoch C, Beroukhim R, Ligon KL, Boehm JS, Hahn WC. Renal medullary carcinomas depend upon loss and are sensitive to proteasome inhibition. Elife 2019. PubMed
  • Chen CH, Bhasin S, Khanna P, Joshi M, Joslin PM, Saxena R, Amin S, Liu S, Sindhu S, Walker SR, Catalano P, Frank DA, Alper SL, Bhasin M, Bhatt RS. Study of Cathepsin B inhibition in VEGFR TKI treated human renal cell carcinoma xenografts. Oncogenesis 2019; 8:15. PubMed
  • Signoretti S, Flaifel A, Chen YB, Reuter VE. Renal Cell Carcinoma in the Era of Precision Medicine: From Molecular Pathology to Tissue-Based Biomarkers. J Clin Oncol 2018. PubMed
  • Krajewski KM, Pedrosa I. Imaging Advances in the Management of Kidney Cancer. J Clin Oncol 2018. PubMed
  • Mahoney KM, Shukla SA, Patsoukis N, Chaudhri A, Browne EP, Arazi A, Eisenhaure TM, Pendergraft WF, Hua P, Pham HC, Bu X, Zhu B, Hacohen N, Fritsch EF, Boussiotis VA, Wu CJ, Freeman GJ. A secreted PD-L1 splice variant that covalently dimerizes and mediates immunosuppression. Cancer Immunol Immunother 2018. PubMed
  • Oser MG, Fonseca R, Chakraborty AA, Brough R, Spektor A, Jennings RB, Flaifel A, Novak JS, Gulati A, Buss E, Younger ST, McBrayer SK, Cowley GS, Bonal DM, Nguyen QD, Brulle-Soumare L, Taylor P, Cairo S, Ryan CJ, Pease EJ, Maratea K, Travers J, Root DE, Signoretti S, Pellman D, Ashton S, Lord CJ, Barry ST, Kaelin WG. Cells Lacking the RB1 Tumor Suppressor Gene are Hyperdependent on Aurora B Kinase for Survival. 2018. PubMed
  • Yip SM, Wells C, Moreira R, Wong A, Srinivas S, Beuselinck B, Porta C, Sim HW, Ernst DS, Rini BI, Yuasa T, Basappa NS, Kanesvaran R, Wood LA, Canil C, Kapoor A, Fu SYF, Choueiri TK, Heng DYC. Checkpoint inhibitors in patients with metastatic renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium. Cancer 2018; 124:3677-3683. PubMed
  • McKay RR, Bossé D, Choueiri TK. Evolving Systemic Treatment Landscape for Patients With Advanced Renal Cell Carcinoma. J Clin Oncol 2018. PubMed
  • Albiges L, Flippot R, Rioux-Leclercq N, Choueiri TK. Non-Clear Cell Renal Cell Carcinomas: From Shadow to Light. J Clin Oncol 2018. PubMed
  • Zhang J, Wu T, Simon J, Takada M, Saito R, Fan C, Liu XD, Jonasch E, Xie L, Chen X, Yao X, Teh BT, Tan P, Zheng X, Li M, Lawrence C, Fan J, Geng J, Liu X, Hu L, Wang J, Liao C, Hong K, Zurlo G, Parker JS, Auman JT, Perou CM, Rathmell WK, Kim WY, Kirschner MW, Kaelin WG, Baldwin AS, Zhang Q. VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma. Science 2018; 361:290-295. PubMed
  • Choueiri TK, Michaelson MD, Posadas EM, Sonpavde GP, McDermott DF, Nixon AB, Liu Y, Yuan Z, Seon BK, Walsh M, Jivani MA, Adams BJ, Theuer CP. An Open Label Phase Ib Dose Escalation Study of TRC105 (Anti-Endoglin Antibody) with Axitinib in Patients with Metastatic Renal Cell Carcinoma. Oncologist 2018. PubMed
  • McDermott DF, Huseni MA, Atkins MB, Motzer RJ, Rini BI, Escudier B, Fong L, Joseph RW, Pal SK, Reeves JA, Sznol M, Hainsworth J, Rathmell WK, Stadler WM, Hutson T, Gore ME, Ravaud A, Bracarda S, Suárez C, Danielli R, Gruenwald V, Choueiri TK, Nickles D, Jhunjhunwala S, Piault-Louis E, Thobhani A, Qiu J, Chen DS, Hegde PS, Schiff C, Fine GD, Powles T. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat Med 2018; 24:749-757. PubMed
  • Choueiri TK, Larkin J, Oya M, Thistlethwaite F, Martignoni M, Nathan P, Powles T, McDermott D, Robbins PB, Chism DD, Cho D, Atkins MB, Gordon MS, Gupta S, Uemura H, Tomita Y, Compagnoni A, Fowst C, di Pietro A, Rini BI. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. Lancet Oncol. 2018; 19:451-460. PubMed
  • Motzer RJ, Escudier B, Powles T, Scheffold C, Choueiri TK. Long-term follow-up of overall survival for cabozantinib versus everolimus in advanced renal cell carcinoma. Br J Cancer 2018. PubMed
  • Kaelin WG. HIF2 Inhibitor Joins the Kidney Cancer Armamentarium. J Clin Oncol 2018; 36:908-910. PubMed
  • Atkins MB, Plimack ER, Puzanov I, Fishman MN, McDermott DF, Cho DC, Vaishampayan U, George S, Olencki TE, Tarazi JC, Rosbrook B, Fernandez KC, Lechuga M, Choueiri TK. Axitinib in combination with pembrolizumab in patients with advanced renal cell cancer: a non-randomised, open-label, dose-finding, and dose-expansion phase 1b trial. Lancet Oncol. 2018; 19:405-415. PubMed
  • Miao D, Margolis CA, Gao W, Voss MH, Li W, Martini DJ, Norton C, Bossé D, Wankowicz SM, Cullen D, Horak C, Wind-Rotolo M, Tracy A, Giannakis M, Hodi FS, Drake CG, Ball MW, Allaf ME, Snyder A, Hellmann MD, Ho T, Motzer RJ, Signoretti S, Kaelin WG, Choueiri TK, Van Allen EM. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science 2018. PubMed
  • Lalani AA, Gray KP, Albiges L, Callea M, Pignon JC, Pal S, Gupta M, Bhatt RS, McDermott DF, Atkins MB, Woude GFV, Harshman LC, Choueiri TK, Signoretti S. Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma and its association with PD-L1 expression. 2017; 8:103428-103436. PubMed
  • Courtney KD, Infante JR, Lam ET, Figlin RA, Rini BI, Brugarolas J, Zojwalla NJ, Lowe AM, Wang K, Wallace EM, Josey JA, Choueiri TK. Phase I Dose-Escalation Trial of PT2385, a First-in-Class Hypoxia-Inducible Factor-2α Antagonist in Patients With Previously Treated Advanced Clear Cell Renal Cell Carcinoma. J Clin Oncol 2017. PubMed
  • Chakraborty AA, Nakamura E, Qi J, Creech A, Jaffe JD, Paulk J, Novak JS, Nagulapalli K, McBrayer SK, Cowley GS, Pineda J, Song J, Wang YE, Carr SA, Root DE, Signoretti S, Bradner JE, Kaelin WG. HIF activation causes synthetic lethality between the VHL tumor suppressor and the EZH1 histone methyltransferase. Sci Transl Med 2017. PubMed
  • Laviolette LA, Mermoud J, Calvo IA, Olson N, Boukhali M, Steinlein OK, Roider E, Sattler EC, Huang D, Teh BT, Motamedi M, Haas W, Iliopoulos O. Negative regulation of EGFR signalling by the human folliculin tumour suppressor protein. Nat Commun 2017; 8:15866. PubMed
  • Cho H, Du X, Rizzi JP, Liberzon E, Chakraborty AA, Gao W, Carvo I, Signoretti S, Bruick RK, Josey JA, Wallace EM, Kaelin WG. On-target efficacy of a HIF-2α antagonist in preclinical kidney cancer models. Nature 2016. PubMed
  • Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, Hammers HJ, Donskov F, Roth BJ, Peltola K, Lee JL, Heng DYC, Schmidinger M, Agarwal N, Sternberg CN, McDermott DF, Aftab DT, Hessel C, Scheffold C, Schwab G, Hutson TE, Pal S, Motzer RJ, . Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016. PubMed
  • Choueiri TK, Escudier B, Powles T, Mainwaring PN, Rini BI, Donskov F, Hammers H, Hutson TE, Lee JL, Peltola K, Roth BJ, Bjarnason GA, Géczi L, Keam B, Maroto P, Heng DY, Schmidinger M, Kantoff PW, Borgman-Hagey A, Hessel C, Scheffold C, Schwab GM, Tannir NM, Motzer RJ, . Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015. PubMed
  • Michaelson MD, McKay RR, Werner L, Atkins MB, Van Allen EM, Olivier KM, Song J, Signoretti S, McDermott DF, Choueiri TK. Phase 2 trial of sunitinib and gemcitabine in patients with sarcomatoid and/or poor-risk metastatic renal cell carcinoma. Cancer 2015. PubMed
  • McKay RR, Lin X, Perkins JJ, Heng DY, Simantov R, Choueiri TK. Prognostic significance of bone metastases and bisphosphonate therapy in patients with renal cell carcinoma. Eur Urol 2014. PubMed
  • Heng DY, Wells JC, Rini BI, Beuselinck B, Lee JL, Knox JJ, Bjarnason GA, Pal SK, Kollmannsberger CK, Yuasa T, Srinivas S, Donskov F, Bamias A, Wood LA, Ernst DS, Agarwal N, Vaishampayan UN, Rha SY, Kim JJ, Choueiri TK. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol 2014. PubMed
  • Gartrell BA, Ying J, Sivendran S, Boucher KM, Choueiri TK, Sonpavde G, Oh WK, Agarwal N, Galsky MD. Pulmonary complications with the use of mTOR inhibitors in targeted cancer therapy: a systematic review and meta-analysis. Target Oncol 2014. PubMed
  • Alimohamed N, Lee JL, Srinivas S, Bjarnason GA, Knox JJ, Mackenzie MJ, Wood L, Vaishampayan UN, Tan MH, Rha SY, Donskov F, Tantravahi S, Kollmannsberger C, North S, Rini BI, Choueiri TK, Heng DY. A population-based overview of sequences of targeted therapy in metastatic renal cell carcinoma. Clin Genitourin Cancer 2014. PubMed
  • Zerbini LF, Bhasin MK, de Vasconcellos JF, Paccez JD, Gu X, Kung AL, Libermann TA. Computational repositioning and preclinical validation of pentamidine for renal cell cancer. Mol Cancer Ther 2014. PubMed
  • Brooks SA, Brannon AR, Parker JS, Fisher JC, Sen O, Kattan MW, Hakimi AA, Hsieh JJ, Choueiri TK, Tamboli P, Maranchie JK, Hinds P, Miller CR, Nielsen ME, Rathmell WK. ClearCode34: A prognostic risk predictor for localized clear cell renal cell carcinoma. Eur Urol 2014. PubMed
  • Escudier B, Michaelson MD, Motzer RJ, Hutson TE, Clark JI, Lim HY, Porfiri E, Zalewski P, Kannourakis G, Staehler M, Tarazi J, Rosbrook B, Cisar L, Hariharan S, Kim S, Rini BI. Axitinib versus sorafenib in advanced renal cell carcinoma: subanalyses by prior therapy from a randomised phase III trial. Br J Cancer 2014; 110:2821-8. PubMed
  • Garcia JA, Hudes GR, Choueiri TK, Stadler WM, Wood LS, Gurtler J, Bhatia S, Joshi A, Hozak RR, Xu Y, Schwartz JD, Thompson JA. A phase 2, single-arm study of ramucirumab in patients with metastatic renal cell carcinoma with disease progression on or intolerance to tyrosine kinase inhibitor therapy. Cancer 2014. PubMed
  • Wagle N, Grabiner BC, Van Allen EM, Hodis E, Jacobus S, Supko JG, Stewart M, Choueiri TK, Gandhi L, Cleary JM, Elfiky AA, Taplin ME, Stack EC, Signoretti S, Loda M, Shapiro GI, Sabatini DM, Lander ES, Gabriel SB, Kantoff PW, Garraway LA, Rosenberg JE. Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib. 2014. PubMed
  • Xu R, Horick N, McGovern FJ, Dahl DM, Feldman AS, Blute ML, Olumi AF, Michaelson MD. Prognostic significance of indeterminate lung nodules in renal cell carcinoma. Urol Oncol 2014; 32:355-61. PubMed
  • Krajewski KM, Nishino M, Franchetti Y, Ramaiya NH, Van den Abbeele AD, Choueiri TK. Intraobserver and interobserver variability in computed tomography size and attenuation measurements in patients with renal cell carcinoma receiving antiangiogenic therapy: implications for alternative response criteria. Cancer 2014; 120:711-21. PubMed
  • Motzer RJ, Jonasch E, Agarwal N, Beard C, Bhayani S, Bolger GB, Chang SS, Choueiri TK, Derweesh IH, Gupta S, Hancock SL, Kim JJ, Kuzel TM, Lam ET, Lau C, Levine EG, Lin DW, Margolin KA, Michaelson MD, Olencki T, Pili R, Plimack ER, Rampersaud EN, Redman BG, Ryan CJ, Sheinfeld J, Sircar K, Somer B, Wang J, Wilder RB, Dwyer MA, Kumar R, . Kidney cancer, version 2.2014. J Natl Compr Canc Netw 2014; 12:175-82. PubMed
  • Zhang PL, Mashni JW, Sabbisetti VS, Schworer CM, Wilson GD, Wolforth SC, Kernen KM, Seifman BD, Amin MB, Geddes TJ, Lin F, Bonventre JV, Hafron JM. Urine kidney injury molecule-1: a potential non-invasive biomarker for patients with renal cell carcinoma. Int Urol Nephrol 2014; 46:379-88. PubMed
  • Schutz FA, Xie W, Donskov F, Sircar M, McDermott DF, Rini BI, Agarwal N, Pal SK, Srinivas S, Kollmannsberger C, North SA, Wood LA, Vaishampayan U, Tan MH, Mackenzie MJ, Lee JL, Rha SY, Yuasa T, Heng DY, Choueiri TK. The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Cancer Database Consortium. Eur Urol 2014; 65:723-30. PubMed
  • Menon S, Dibble CC, Talbott G, Hoxhaj G, Valvezan AJ, Takahashi H, Cantley LC, Manning BD. Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome. Cell 2014; 156:771-85. PubMed
  • Beddy P, Genega EM, Ngo L, Hindman N, Wei J, Bullock A, Bhatt RS, Atkins MB, Pedrosa I. Tumor necrosis on magnetic resonance imaging correlates with aggressive histology and disease progression in clear cell renal cell carcinoma. Clin Genitourin Cancer 2014; 12:55-62. PubMed
  • Molina AM, Hutson TE, Larkin J, Gold AM, Wood K, Carter D, Motzer R, Michaelson MD. A phase 1b clinical trial of the multi-targeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC). Cancer Chemother Pharmacol 2014; 73:181-9. PubMed
  • Li L, Shen C, Nakamura E, Ando K, Signoretti S, Beroukhim R, Cowley GS, Lizotte P, Liberzon E, Bair S, Root DE, Tamayo P, Tsherniak A, Cheng SC, Tabak B, Jacobsen A, Hakimi AA, Schultz N, Ciriello G, Sander C, Hsieh JJ, Kaelin WG. SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer. Cancer Cell 2013; 24:738-50. PubMed
  • Liu M, Roth A, Yu M, Morris R, Bersani F, Rivera MN, Lu J, Shioda T, Vasudevan S, Ramaswamy S, Maheswaran S, Diederichs S, Haber DA. The IGF2 intronic miR-483 selectively enhances transcription from IGF2 fetal promoters and enhances tumorigenesis. Genes Dev 2013; 27:2543-8. PubMed
  • Akhavanfard S, Vargas SO, Han M, Nitta M, Chang CB, Le LP, Fazlollahi L, Nguyen Q, Ma Y, Cosper A, Dias-Santagata D, Han JY, Bergethon K, Borger DR, Ellisen LW, Pomeroy SL, Haber DA, Iafrate AJ, Rivera MN. Inactivation of the tumor suppressor WTX in a subset of pediatric tumors. Genes Chromosomes Cancer 2014; 53:67-77. PubMed
  • Chen JL, Appelbaum DE, Kocherginsky M, Cowey CL, Rathmell WK, McDermott DF, Stadler WM. FDG-PET as a predictive biomarker for therapy with everolimus in metastatic renal cell cancer. Cancer Med 2013; 2:545-52. PubMed
  • Dandamudi UB, Ghebremichael M, Sosman JA, Clark JI, McDermott DF, Atkins MB, Dutcher JP, Urba WJ, Regan MM, Puzanov I, Crocenzi TS, Curti BD, Vaishampayan UN, Crosby NA, Margolin KA, Ernstoff MS. A phase II study of bevacizumab and high-dose interleukin-2 in patients with metastatic renal cell carcinoma: a Cytokine Working Group (CWG) study. J Immunother ; 36:490-5. PubMed
  • Choueiri TK, Fay AP, Gagnon R, Lin Y, Bahamon B, Brown V, Rosenberg JE, Hutson TE, Baker-Neblett KL, Carpenter C, Liu Y, Pandite L, Signoretti S. The role of aberrant VHL/HIF pathway elements in predicting clinical outcome to pazopanib therapy in patients with metastatic clear-cell renal cell carcinoma. Clin Cancer Res 2013; 19:5218-26. PubMed
  • Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J, Nathan P, Staehler M, de Souza P, Merchan JR, Boleti E, Fife K, Jin J, Jones R, Uemura H, De Giorgi U, Harmenberg U, Wang J, Sternberg CN, Deen K, McCann L, Hackshaw MD, Crescenzo R, Pandite LN, Choueiri TK. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med 2013; 369:722-31. PubMed
  • Kroeger N, Xie W, Lee JL, Bjarnason GA, Knox JJ, Mackenzie MJ, Wood L, Srinivas S, Vaishamayan UN, Rha SY, Pal SK, Yuasa T, Donskov F, Agarwal N, Kollmannsberger CK, Tan MH, North SA, Rini BI, Choueiri TK, Heng DY. Metastatic non-clear cell renal cell carcinoma treated with targeted therapy agents: characterization of survival outcome and application of the International mRCC Database Consortium criteria. Cancer 2013; 119:2999-3006. PubMed
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Kidney SPORE

PI: David F. McDermott, MD (BIDMC)
Co-PI: William G. Kaelin, Jr., MD (DFCI)

SPORE Projects

Targeting HIF2 and VHL Synthetic Lethal Injections in Kidney Cancer
Co-Leaders: William G. Kaelin, Jr., MD (DFCI); Toni K. Choueiri, MD (DFCI); Sabina Signoretti, MD (BWH)

Optimal Targeting of the PD-1/PD-L1 Pathway in MRCC
Co-Leaders: Catherine J. Wu, MD (DFCI); Michael Atkins, MD (GU); Sabina Signoretti, MD (BWH)

HHLa2 as a Therapeutic Target in RCC
Co-Leaders: David F. McDermott, MD (BIDMC); Gordon J. Freeman, PhD (DFCI)

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