Dan Theodorescu, MD, PhD

Professional Titles

• Distinguished Professor Surgery-Urology
• Director, University of Colorado Comprehensive Cancer Center
• Co-Editor in Chief, Bladder Cancer
• Distinguished Professor - Pharmacology

Recognitions

• Inventor of the Year, University of Colorado (2011)
  
• Professor Emeritus, Department of Urology, University of Virginia (2010)
  
• Elected, American Association of Genitourinary Surgeons (AAGUS) (2008)
• Elected, American Society for Clinical Investigation (ASCI) (2006)
• Resident Teaching Award, Department of Urology, University of Virginia (1999)
  
• Edwin Beer Award , New York Academy of Medicine (1998)
  
• Young Investigator Award , Society for Basic Urologic Research (1998)
  
• Kimmel Foundation Scholar, Kimmel Foundation (1997)
  
• Elected, Elected to American Surgical Association (ASA) (2012)
• Elected, National Academy of Medicine (NAM) (2014)
• Barringer Medal for Outstanding Contributions, American Association of Genitourinary Surgeons (AAGUS) (2015)

Research Interests

Working on a disease that has seen few advances in the last 30 years, Theodorescu has emerged as a leading translational bladder cancer researcher. Theodorescu is known for his work on the molecular mechanisms underlying bladder cancer and tools that determine drug response as well as discovery of new drugs for several cancer types. Examples include discovery of genes that regulate tumor growth and metastasis (RhoGDI2, CD24, AGL, GON4L) in bladder and other cancers and novel biomarkers (DNA/NGS, RNA and proteomic) and concepts for precision therapeutic approaches such as the COXEN principle, that are currently being tested in national (SWOG) clinical trials. He led the discovery and development of a “first in class” RalGTPase inhibitor as a new therapeutic in several human cancer types which is now in commercial development. Recent efforts in our lab have focused on understanding the biology of Telomerase reverse transcriptase (TERT) and using that knowledge to develop novel inhibitors to this critical protein in cancer. Finally, active efforts are currently aimed at identifying immune system agonists or antagonists that modulate tumor behavior in vivo as well as the identification of novel combination therapies that enhance the effectiveness of checkpoint and other immunotherapy.

Publications

• Cathro HP, Smolkin ME, Theodorescu D, Jo VY, Ferrone S, Frierson HF, Jr. Relationship between HLA class I antigen processing machinery component expression and the clinicopathologic characteristics of bladder carcinomas. Cancer Immunol Immunother. 2010;59:465-72.
• Good DM, Zurbig P, Argiles A, Bauer HW, Behrens G, Coon JJ, Dakna M, Decramer S, Delles C, Dominiczak AF, Ehrich JH, Eitner F, Fliser D, Frommberger M, Ganser A, Girolami MA, Golovko I, Gwinner W, Haubitz M, Herget-Rosenthal S, Jankowski J, Jahn H, Jerums G, Julian BA, Kellmann M, Kliem V, Kolch W, Krolewski AS, Luppi M, Massy Z, Melter M, Neususs C, Novak J, Peter K, Rossing K, Rupprecht H, Schanstra JP, Schiffer E, Stolzenburg JU, Tarnow L, Theodorescu D, Thongboonkerd V, Vanholder R, Weissinger EM, Mischak H, Schmitt-Kopplin P. Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease. Mol Cell Proteomics. 2010;9:2424-37.
• Hansel DE, Platt E, Orloff M, Harwalker J, Sethu S, Hicks JL, De Marzo A, Steinle RE, Hsi ED, Theodorescu D, Ching CB, Eng C. Mammalian target of rapamycin (mTOR) regulates cellular proliferation and tumor growth in urothelial carcinoma. Am J Pathol. 2010;176:3062-72.
• Harding MA, Theodorescu D. RhoGDI signaling provides targets for cancer therapy. Eur J Cancer. 2010;46:1252-9.
• Jerde TJ, Wu Z, Theodorescu D, Bushman W. Regulation of phosphatase homologue of tensin protein expression by bone morphogenetic proteins in prostate epithelial cells. Prostate. 2010.
• Krupski TL, Stukenborg GJ, Moon K, Theodorescu D. The relationship of palliative transurethral resection of the prostate with disease progression in patients with prostate cancer. BJU Int. 2010;106:1477-83.
• Lee JK, Coutant C, Kim YC, Qi Y, Theodorescu D, Symmans WF, Baggerly K, Rouzier R, Pusztai L. Prospective comparison of clinical and genomic multivariate predictors of response to neoadjuvant chemotherapy in breast cancer. Clin Cancer Res. 2010;16:711-8.
• Mischak H, Allmaier G, Apweiler R, Attwood T, Baumann M, Benigni A, Bennett SE, Bischoff R, Bongcam-Rudloff E, Capasso G, Coon JJ, D'Haese P, Dominiczak AF, Dakna M, Dihazi H, Ehrich JH, Fernandez-Llama P, Fliser D, Frokiaer J, Garin J, Girolami M, Hancock WS, Haubitz M, Hochstrasser D, Holman RR, Ioannidis JP, Jankowski J, Julian BA, Klein JB, Kolch W, Luider T, Massy Z, Mattes WB, Molina F, Monsarrat B, Novak J, Peter K, Rossing P, Sanchez-Carbayo M, Schanstra JP, Semmes OJ, Spasovski G, Theodorescu D, Thongboonkerd V, Vanholder R, Veenstra TD, Weissinger E, Yamamoto T, Vlahou A. Recommendations for biomarker identification and qualification in clinical proteomics. Sci Transl Med. 2010;2:46ps2.
• Pollard C, Smith SC, Theodorescu D. Molecular genesis of non-muscle-invasive urothelial carcinoma (NMIUC). Expert Rev Mol Med. 2010;12:e10.
• Smith SC, Baras AS, Lee JK, Theodorescu D. The COXEN principle: translating signatures of in vitro chemosensitivity into tools for clinical outcome prediction and drug discovery in cancer. Cancer Res. 2010;70:1753-8.
• Wang H, Owens C, Chandra N, Conaway MR, Brautigan DL, Theodorescu D. Phosphorylation of RalB is important for bladder cancer cell growth and metastasis. Cancer Res. 2010;70:8760-9.
• Wilson SS, Theodorescu D. Rare bladder tumors: caveat emptor. Oncology. 2010;24:838.
• Wu Z, Owens C, Chandra N, Popovic K, Conaway M, Theodorescu D. RalBP1 is necessary for metastasis of human cancer cell lines. Neoplasia. 2010;12:1003-12.
• Said N, Smith S, Sanchez-Carbayo M, Theodorescu D. Tumor endothelin-1 enhances metastatic colonization of the lung in mouse xenograft models of bladder cancer. J Clin Invest. 2011;121:132-47.
• Smith SC, Baras AS, Dancik G, Ru Y, Ding KF, Moskaluk CA, Fradet Y, Lehmann J, Stockle M, Hartmann A, Lee JK, Theodorescu D. A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment. Lancet Oncol. 2011;12:137-43.
• Smith SC, Havaleshko DM, Moon K, Baras AS, Lee J, Bekiranov S, Burke DJ, Theodorescu D. Use of yeast chemigenomics and COXEN informatics in preclinical evaluation of anticancer agents. Neoplasia. 2011;13:72-80
• Thomas S, Overdevest JB, Nitz MD, Williams PD, Owens CR, Sanchez-Carbayo M, Frierson HF, Schwartz MA, Theodorescu D. Src and Caveolin-1 Reciprocally Regulate Metastasis via a Common Downstream Signaling Pathway in Bladder Cancer. Cancer Res. 2011;71:832-41.
• Smith SC and Theodorescu, D. 2010. Predictive markers for therapeutic response in urothelial carcinoma. Textbook of Bladder Cancer, Edited by: V. Lokeshwar, Springer Press.
• Cote R and Theodorescu, D. 2010. Molecular Biology and Prognostic Factors of Bladder cancer. 4th edition of the Comprehension Textbook of Genitourinary Oncology, Edited by: Scardino, Linehan, Vogelzang, Springer Press
• Said N and Theodorescu D. 2011. Molecular Pathogenesis of Lung Metastasis. Signalling Pathways and Molecular Mediators in Metastasis. Editor: Alessandro Fatatis, Spinger Press.
• Marchioni, L and Theodorescu D. 2011. Molecular Pathogenesis of Bladder Cancer. Textbook of Urologic Pathology, Edited by: D Hansel, Springer Press.
• Burns, J.B., Bassignani, S.C., Krupski, S., Theodorescu, D., Schenkman, N. 2010. Radiation Exposure During Computed Tomography-Guided Cryoablation of Renal Masses. ASCO (submitted).
• Ferriss, J.S., Kim, Y. Theodorescu, D. Duska, L. R. Lee, J. 2010. A gene expression algorithm for the prediction of platinum sensitivity in ovarian cancer. ASCO (submitted).
• Cho, J.B., Smith, S.C., Lee, J., Theodorescu, D., Laurent-Puig, P. 2010. In vitro-based COXEN biomarker model predicts outcome in metastatic colorectal cancer patients treated with cetuximab. American Association for Cancer Research Abstr 6795
• Said, N., Theodorescu, D. 2010. The metastasis suppressor RhoGDI2 suppresses expression of Endothelin axis is critical for metastasis. American Association for Cancer Research Abstr 4529
• Smith SC, Kristiansen G, Hansel DE, Theodorescu D. 2010. Evaluation of CD24 expression in matched primary and metastatic muscle invasive urothelial carcinoma tissues. United States and Canadian Academy of Pathology Annual Meeting. Abstr 147.
• Baras AS, Smith SC, Moskaluk CA, Frierson HF, Theodorescu D. 2010. Derivation and Independent Validation of a Gene Expression-Based Predictor for Post-Cystectomy Recurrence in Nodal Negative Muscle Invasive Urothelial Carcinoma. United States and Canadian Academy of Pathology Annual Meeting. Abstr 219.
• Smith SC, Hansel DE, Frierson HF, Theodorescu D. 2010. The Prognostic Value of the Metastasis Suppressor, RhoGDI2, in Muscle Invasive Urothelial Carcinoma. United States and Canadian Academy of Pathology Annual Meeting. Abstr 146.
• Theodorescu, D, Schiffer, E, Vlahou, A, Stravodimos, K, Geschwend, J, Stolzenburg, J, Mischak, H, Bauer, H. 2010. Clinical Proteomics-Ready for Prime Time in Urological Cancer Diagnostics. 62nd Congress of the German Urologic Society.
• Theodorescu, D. 2010. Role of Versican in Bladder Cancer Metastasis to the Lungs. Joint MRS-AACR Conference on Metastasis and the Tumor Microenvironment
• Said N, Smith S, Sanchez-Carbayo M, Theodorescu D. Tumor endothelin-1 enhances metastatic colonization of the lung in mouse xenograft models of bladder cancer. J Clin Invest. 2011;121:132-47.
• Smith SC, Baras AS, Dancik G, Ru Y, Ding KF, Moskaluk CA, Fradet Y, Lehmann J, Stockle M, Hartmann A,Lee JK, Theodorescu D. A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment. Lancet Oncol. 2011;12:137-43.
• Smith SC, Havaleshko DM, Moon K, Baras AS, Lee J, Bekiranov S, Burke DJ, Theodorescu D. Use of yeast chemigenomics and COXEN informatics in preclinical evaluation of anticancer agents. Neoplasia. 2011;13:72-80.
• Thomas S, Overdevest JB, Nitz MD, Williams PD, Owens CR, Sanchez-Carbayo M, Frierson HF, Schwartz MA, Theodorescu D. Src and Caveolin-1 Reciprocally Regulate Metastasis via a Common Downstream Signaling Pathway in Bladder Cancer. Cancer Res. 2011;71:832-41.
• Overdevest JB, Nitz MD, Owens CR, Frierson HF, Theodorescu D. CD24 offers a therapeutic target for control of bladder cancer metastasis based on a requirement for lung colonization. Cancer Res 2011 Jun 1;71(11):3802- 11.
• Nitz MD, Williams PD, Owens CR, Frierson HF, Theodorescu D. Characterization of RREB1 transcription factor splice variants in human cancer. Am J Pathol. 2011 Jul;179(1):477-86
• Ru Y, Dancik GM, Theodorescu D. Biomarkers for prognosis and treatment selection in advanced bladder cancer patients. Curr Opin Urol. 2011;21(5):420-7.
• Aisner DL, Theodorescu D. Genetic testing for metastasis: potential for improved cancer treatment. Future Oncol. 2011;7(6):697-701.
• Yaoting G, Guangwu G, Yi H, Xueda H, et al. Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder. Nat Genet, 2011 Aug 7. doi: 10.1038/ng.907
• Dancik G, Aisner D, Theodorescu D. A 20 gene model for predicting nodal involvement in bladder cancer patients with muscle invasive tumors. PLoS Curr. 2011 Aug 11;3:RRN1248.
• Dancik G, Ru Y, Theodorescu D. A framework for selecting clinically relevant tumor cell lines via their molecular similarity with human cancers. Cancer Res 2012
• Cekic C, Sag D, Li Y, Theodorescu D, Strieter RM, Linden J. Adenosine A2B receptor blockade slows growth of bladder and breast tumors" has been accepted for publication in J Immunol 2012
• Williams PD, Lee JK, Theodorescu D. Cyclophilin-B expression is associated with in vitro radioresistance and clinical outcome after radiotherapy Neoplasia 2012
• Ferriss SJ, Kim Y-C, Duska L, Birrer M, Theodorescu D, Lee JK. Multi-gene Expression Predictors of Single Drug Responses to Adjuvant Chemotherapy in Ovarian Carcinoma: Predicting Platinum Resistance. Plos One 2012 (
• Said N, Sanchez-Carbayo M, Theodorescu D. RhoGDI2 suppresses metastasis via reduction of versican expression and macrophage infiltration. J Clin Invest. 2012
• Overdevest JB, Nitz MD, Owens CR, Frierson HF, Theodorescu D. CD24 expression leads to sex-specific differences in tumorigenesis and metastasis in a carcinogenesis model of urothelial cancer. Proc Natl Acad Sci U S A. 2012
• Griner EM, Nitz MD, Owens CR, Frierson HF, Theodorescu D. PKCa phosphorylation of RhoGDI2 at Ser 31 disrupts interactions with Rac1 and decreases GDI activity. Oncogene 2012.
• DeGraff DJ, Duska L, Birrer M, Theodorescu D, Lee JK. Loss of the Urothelial Differentiation Marker FOXA1 is Associated With High Grade, Late Stage Bladder Cancer and Increased Tumor Proliferation Plos One 2012
• Dancik GM, Owens CR, Iczkowski KA, Theodorescu D. A cell of origin gene signature indicates human bladder cancer has distinct cellular progenitors. Stem Cells. 2013 Dec 19. [Epub ahead of print] PubMed PMID: 24357085

Professional Memberships

• American College of Surgeons (ACS), Member
• Society for Urologic Oncology (SUO), Member
• American Urological Association (AUA), Member
• American Society for Clinical Oncology (ASCO), Member
• American Association for Cancer Research (AACR), Member
• Society for Basic Urologic Research (SBUR), Member
• National Academy of Medicine (NAM), Elected Member
• American Surgical Association (ASA), Elected Member
• American Association of Genitourinary Surgeons (AAGUS), Elected Member
• American Society for Clinical Investigation (ASCI), Elected Member

Practice Locations

Hospital Affiliation

• University of Colorado Hospital

Center Affiliations

• University of Colorado Cancer Center

Specialty Information

Specialties

• Urology, Board Certification (1999, 2007)