Photo of Steven P. Balk,  MD, PhD

Steven P. Balk, MD, PhD

Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center
Phone: (617) 735-2065
Fax: (617) 667-0610

Steven P. Balk, MD, PhD

Beth Israel Deaconess Medical Center


  • Professor, Medicine, Harvard Medical School
  • Staff Physician, Hematology/Oncology, Beth Israel Deaconess Medical Center



  • Member, Center Scientific Council

Research Abstract

The major focus of the lab is on the molecular basis of prostate cancer development and progression. The androgen receptor, which is a member of the steroid hormone receptor superfamily, plays a major role in prostate cancer. We have identified mutations in the androgen receptor that contribute to prostate cancer progression and are characterizing androgen receptor interacting proteins. We have also determined that the platelet derived growth factor receptor contributes to prostate cancer and are attempting to define other important growth factor-receptor interactions that may be useful therapeutic targets. Finally, efforts are underway to develop murine transgenic and gene knockout models of PCa. A second interest in the lab is a novel T cell population termed NK T cells and the MHC class I-like CD1d protein they recognize. These cells appear to have an important immunoregulatory function and we are determining the role they play in viral infections and anti-tumor



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  • Gerrin SJ, Sowalsky AG, Balk SP, Ye H. Mutation profiling indicates high grade prostatic intraepithelial neoplasia as distant precursors of adjacent invasive prostatic adenocarcinoma. Prostate 2016. PubMed
  • Li Z, Alyamani M, Li J, Rogacki K, Abazeed M, Upadhyay SK, Balk SP, Taplin ME, Auchus RJ, Sharifi N. Redirecting abiraterone metabolism to fine-tune prostate cancer anti-androgen therapy. Nature 2016; 533:547-51. PubMed
  • Ma F, Ye H, He HH, Gerrin SJ, Chen S, Tanenbaum BA, Cai C, Sowalsky AG, He L, Wang H, Balk SP, Yuan X. SOX9 drives WNT pathway activation in prostate cancer. J Clin Invest 2016. PubMed
  • Gao S, Ye H, Gerrin S, Wang H, Sharma A, Chen S, Patnaik A, Sowalsky AG, Voznesensky O, Han W, Yu Z, Mostaghel E, Nelson PS, Taplin ME, Balk SP, Cai C. ErbB2 Signaling Increases Androgen Receptor Expression in Abiraterone-Resistant Prostate Cancer. Clin Cancer Res 2016. PubMed
  • Liu X, Han W, Gulla S, Simon NI, Gao Y, Cai C, Yang H, Zhang X, Liu J, Balk SP, Chen S. Protein phosphatase 1 suppresses androgen receptor ubiquitylation and degradation. 2015. PubMed
  • Taplin ME, Balk SP. Has the Time Arrived for Biomarker-Directed Therapy in Castration-Resistant Prostate Cancer? JAMA Oncol 2015. PubMed
  • Tamae D, Mostaghel E, Montgomery B, Nelson PS, Balk SP, Kantoff PW, Taplin ME, Penning TM. The DHEA-sulfate depot following P450c17 inhibition supports the case for AKR1C3 inhibition in high risk localized and advanced castration resistant prostate cancer. Chem. Biol. Interact. 2015. PubMed
  • Sowalsky AG, Sager R, Schaefer RJ, Bratslavsky G, Pandolfi PP, Balk SP, Kotula L. Loss of Wave1 gene defines a subtype of lethal prostate cancer. 2015; 6:12383-91. PubMed
  • Hsieh CL, Botta G, Gao S, Li T, Van Allen EM, Treacy DJ, Cai C, He HH, Sweeney CJ, Brown M, Balk SP, Nelson PS, Garraway LA, Kantoff PW. PLZF, a tumor suppressor genetically lost in metastatic castration-resistant prostate cancer, is a mediator of resistance to androgen deprivation therapy. Cancer Res 2015. PubMed
  • Chen EJ, Sowalsky AG, Gao S, Cai C, Voznesensky O, Schaefer R, Loda M, True LD, Ye H, Troncoso P, Lis RL, Kantoff PW, Montgomery RB, Nelson PS, Bubley GJ, Balk SP, Taplin ME. Abiraterone treatment in castration-resistant prostate cancer selects for progesterone responsive mutant androgen receptors. Clin Cancer Res 2015. PubMed
  • Plymate SR, Bhatt RS, Balk SP. Taxane resistance in prostate cancer mediated by AR-independent GATA2 regulation of IGF2. Cancer Cell 2015; 27:158-9. PubMed
  • Lu J, Lonergan PE, Nacusi LP, Wang L, Schmidt LJ, Sun Z, Van der Steen T, Boorjian SA, Kosari F, Vasmatzis G, Klee GG, Balk SP, Huang H, Wang C, Tindall DJ. The cistrome and gene signature of androgen receptor splice variants in castration resistant prostate cancer cells. J Urol 2015. PubMed
  • Sowalsky AG, Xia Z, Wang L, Zhao H, Chen S, Bubley GJ, Balk SP, Li W. Whole transcriptome sequencing reveals extensive unspliced mRNA in metastatic castration-resistant prostate cancer. Mol Cancer Res 2015. PubMed
  • Cai C, He HH, Gao S, Chen S, Yu Z, Gao Y, Chen S, Chen MW, Zhang J, Ahmed M, Wang Y, Metzger E, Schüle R, Liu XS, Brown M, Balk SP. Lysine-specific demethylase 1 has dual functions as a major regulator of androgen receptor transcriptional activity. Cell Rep 2014; 9:1618-27. PubMed
  • Taplin ME, Montgomery B, Logothetis CJ, Bubley GJ, Richie JP, Dalkin BL, Sanda MG, Davis JW, Loda M, True LD, Troncoso P, Ye H, Lis RT, Marck BT, Matsumoto AM, Balk SP, Mostaghel EA, Penning TM, Nelson PS, Xie W, Jiang Z, Haqq CM, Tamae D, Tran N, Peng W, Kheoh T, Molina A, Kantoff PW. Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate in patients with localized high-risk prostate cancer: results of a randomized phase II neoadjuvant study. J Clin Oncol 2014. PubMed
  • Chin YR, Yuan X, Balk SP, Toker A. PTEN-deficient tumors depend on AKT2 for maintenance and survival. 2014. PubMed
  • Yu Z, Cai C, Gao S, Simon NI, Shen HC, Balk SP. Galeterone prevents androgen receptor binding to chromatin and enhances degradation of mutant androgen receptor. Clin Cancer Res 2014. PubMed
  • Yuan X, Cai C, Chen S, Chen S, Yu Z, Balk SP. Androgen receptor functions in castration-resistant prostate cancer and mechanisms of resistance to new agents targeting the androgen axis. Oncogene 2014. PubMed
  • Sun T, Wang X, He HH, Sweeney CJ, Liu SX, Brown M, Balk S, Lee GS, Kantoff PW. MiR-221 promotes the development of androgen independence in prostate cancer cells via downregulation of HECTD2 and RAB1A. Oncogene 2014. PubMed
  • Hsieh CL, Fei T, Chen Y, Li T, Gao Y, Wang X, Sun T, Sweeney CJ, Lee GS, Chen S, Balk SP, Liu XS, Brown M, Kantoff PW. Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation. Proc Natl Acad Sci U S A 2014. PubMed
  • Balk SP. Androgen receptor functions in prostate cancer development and progression. Asian J. Androl. 2014. PubMed
  • Yu Z, Chen S, Sowalsky AG, Voznesensky OS, Mostaghel EA, Nelson PS, Cai C, Balk SP. Rapid induction of androgen receptor splice variants by androgen deprivation in prostate cancer. Clin Cancer Res 2014; 20:1590-600. PubMed
  • Mostaghel EA, Nelson PS, Lange P, Lin DW, Taplin ME, Balk S, Ellis W, Kantoff P, Marck B, Tamae D, Matsumoto AM, True LD, Vessella R, Penning T, Hunter Merrill R, Gulati R, Montgomery B. Targeted androgen pathway suppression in localized prostate cancer: a pilot study. J Clin Oncol 2014; 32:229-37. PubMed
  • Liu F, Zhang X, Weisberg E, Chen S, Hur W, Wu H, Zhao Z, Wang W, Mao M, Cai C, Simon NI, Sanda T, Wang J, Look AT, Griffin JD, Balk SP, Liu Q, Gray NS. Discovery of a selective irreversible BMX inhibitor for prostate cancer. ACS Chem Biol 2014. PubMed
  • Wang H, He L, Ma F, Regan MM, Balk SP, Richardson AL, Yuan X. SOX9 regulates low density lipoprotein receptor-related protein 6 (LRP6) and T-cell factor 4 (TCF4) expression and Wnt/β-catenin activation in breast cancer. J Biol Chem 2013; 288:6478-87. PubMed
  • Cai C, Wang H, He HH, Chen S, He L, Ma F, Mucci L, Wang Q, Fiore C, Sowalsky AG, Loda M, Liu XS, Brown M, Balk SP, Yuan X. ERG induces androgen receptor-mediated regulation of SOX9 in prostate cancer. J Clin Invest 2013; 123:1109-22. PubMed
  • Sowalsky AG, Ye H, Bubley GJ, Balk SP. Clonal progression of prostate cancers from Gleason grade 3 to grade 4. Cancer Res 2013; 73:1050-5. PubMed
  • Xu K, Wu ZJ, Groner AC, He HH, Cai C, Lis RT, Wu X, Stack EC, Loda M, Liu T, Xu H, Cato L, Thornton JE, Gregory RI, Morrissey C, Vessella RL, Montironi R, Magi-Galluzzi C, Kantoff PW, Balk SP, Liu XS, Brown M. EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent. Science 2012; 338:1465-9. PubMed
  • Shen HC, Shanmugasundaram K, Simon NI, Cai C, Wang H, Chen S, Balk SP, Rigby AC. In silico discovery of androgen receptor antagonists with activity in castration resistant prostate cancer. Mol Endocrinol 2012; 26:1836-46. PubMed
  • Lynch L, Nowak M, Varghese B, Clark J, Hogan AE, Toxavidis V, Balk SP, O'Shea D, O'Farrelly C, Exley MA. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity 2012; 37:574-87. PubMed
  • Wang H, Xu Y, Fang Z, Chen S, Balk SP, Yuan X. Doxycycline regulated induction of AKT in murine prostate drives proliferation independently of p27 cyclin dependent kinase inhibitor downregulation. PLoS ONE 2012; 7:e41330. PubMed
  • Exley MA, Wilson B, Balk SP. Isolation and functional use of human NKT cells. Curr Protoc Immunol 2010; Chapter 14:Unit 14.11. PubMed
  • Jiang X, Chen S, Asara JM, Balk SP. Phosphoinositide-3-kinase pathway activation in PTEN deficient prostate cancer cells is independent of receptor tyrosine kinases and mediated by the p110{beta} and p110{delta} catalytic subunits. J Biol Chem 2010; 285:14980-9. PubMed
  • Porcelli S, Brenner MB, Greenstein JL, Terhorst C, Balk SP, Bleicher PA. Pillars Article: Recognition of Cluster of Differentiation 1 Antigens by Human CD4-CD8- CytolyticT Lymphocyte. Nature. 1989. 341: 447-450. J Immunol 2010; 184:3306-9. PubMed
  • Nowak M, Lynch L, Yue S, Ohta A, Sitkovsky M, Balk SP, Exley MA. The A2aR adenosine receptor controls cytokine production in iNKT cells. Eur J Immunol 2010; 40:682-7. PubMed
  • Yue SC, Nowak M, Shaulov-Kask A, Wang R, Yue D, Balk SP, Exley MA. Direct CD1d-mediated stimulation of APC IL-12 production and protective immune response to virus infection in vivo. J Immunol 2009; 184:268-76. PubMed
  • Nowak M, Arredouani MS, Tun-Kyi A, Schmidt-Wolf I, Sanda MG, Balk SP, Exley MA. Defective NKT cell activation by CD1d+ TRAMP prostate tumor cells is corrected by interleukin-12 with alpha-galactosylceramide. PLoS ONE 2010; 5:e11311. PubMed
  • Taplin ME, Regan MM, Ko YJ, Bubley GJ, Duggan SE, Werner L, Beer TM, Ryan CW, Mathew P, Tu SM, Denmeade SR, Oh WK, Sartor O, Mantzoros CS, Rittmaster R, Kantoff PW, Balk SP. Phase II study of androgen synthesis inhibition with ketoconazole, hydrocortisone, and dutasteride in asymptomatic castration-resistant prostate cancer. Clin Cancer Res 2009; 15:7099-105. PubMed
  • Lu B, Maqsodi B, Yang W, McMaster GK, Perner S, Regan M, Bubley GJ, Balk SP, Rubin M, Sanda MG. Detection of TMPRSS2-ERG fusion gene expression in prostate cancer specimens by a novel assay using branched DNA. Urology 2009; 74:1156-61. PubMed
  • Sartor O, Nakabayashi M, Taplin ME, Ross RW, Kantoff PW, Balk SP, Oh WK. Activity of dutasteride plus ketoconazole in castration-refractory prostate cancer after progression on ketoconazole alone. Clin Genitourin Cancer 2009; 7:E90-2. PubMed
  • Chen S, Kesler CT, Paschal BM, Balk SP. Androgen receptor phosphorylation and activity are regulated by an association with protein phosphatase 1. J Biol Chem 2009; 284:25576-84. PubMed
  • Cai C, Wang H, Xu Y, Chen S, Balk SP. Reactivation of androgen receptor-regulated TMPRSS2:ERG gene expression in castration-resistant prostate cancer. Cancer Res 2009; 69:6027-32. PubMed
  • Wang Q, Li W, Zhang Y, Yuan X, Xu K, Yu J, Chen Z, Beroukhim R, Wang H, Lupien M, Wu T, Regan MM, Meyer CA, Carroll JS, Manrai AK, Jänne OA, Balk SP, Mehra R, Han B, Chinnaiyan AM, Rubin MA, True L, Fiorentino M, Fiore C, Loda M, Kantoff PW, Liu XS, Brown M. Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell 2009; 138:245-56. PubMed
  • Cai C, Portnoy DC, Wang H, Jiang X, Chen S, Balk SP. Androgen receptor expression in prostate cancer cells is suppressed by activation of epidermal growth factor receptor and ErbB2. Cancer Res 2009; 69:5202-9. PubMed
  • Shen HC,Balk SP. Development of androgen receptor antagonists with promising activity in castration-resistant prostate cancer. Cancer Cell 2009; 15:461-3. PubMed
  • Sun T, Wang Q, Balk S, Brown M, Lee GS, Kantoff P. The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines. Cancer Res 2009; 69:3356-63. PubMed
  • Yuan X,Balk SP. Mechanisms mediating androgen receptor reactivation after castration. Urol Oncol 2008; 27:36-41. PubMed
  • Hur W,Velentza A,Kim S,Flatauer L,Jiang X,Valente D,Mason DE,Suzuki M,Larson B,Zhang J,Zagorska A,Didonato M,Nagle A,Warmuth M,Balk SP,Peters EC,Gray NS. Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase. Bioorg Med Chem Lett 2008; 18:5916-9. PubMed
  • Song W,van der Vliet HJ,Tai YT,Prabhala R,Wang R,Podar K,Catley L,Shammas MA,Anderson KC,Balk SP,Exley MA,Munshi NC. Generation of antitumor invariant natural killer T cell lines in multiple myeloma and promotion of their functions via lenalidomide: a strategy for immunotherapy. Clin Cancer Res 2008; 14:6955-62. PubMed
  • Hodgson MC,Shen HC,Hollenberg AN,Balk SP. Structural basis for nuclear receptor corepressor recruitment by antagonist-liganded androgen receptor. Mol Cancer Ther 2008; 7:3187-94. PubMed
  • Kaur R,Yuan X,Lu ML,Balk SP. Increased PAK6 expression in prostate cancer and identification of PAK6 associated proteins. Prostate 2008; 68:1510-6. PubMed
  • Bhatt RS, Landis DM, Zimmer M, Torregrossa J, Chen S, Sukhatme VP, Iliopoulos O, Balk S, Bubley GJ. Hypoxia-inducible factor-2alpha: effect on radiation sensitivity and differential regulation by an mTOR inhibitor. BJU Int 2008; 102:358-63. PubMed
  • Exley MA,Hou R,Shaulov A,Tonti E,Dellabona P,Casorati G,Akbari O,Akman HO,Greenfield EA,Gumperz JE,Boyson JE,Balk SP,Wilson SB. Selective activation, expansion, and monitoring of human iNKT cells with a monoclonal antibody specific for the TCR alpha-chain CDR3 loop. Eur J Immunol 2008; 38:1756-66. PubMed
  • Bao BY,Chuang BF,Wang Q,Sartor O,Balk SP,Brown M,Kantoff PW,Lee GS. Androgen receptor mediates the expression of UDP-glucuronosyltransferase 2 B15 and B17 genes. Prostate 2008; 68:839-48. PubMed
  • van der Vliet HJ,Wang R,Yue SC,Koon HB,Balk SP,Exley MA. Circulating myeloid dendritic cells of advanced cancer patients result in reduced activation and a biased cytokine profile in invariant NKT cells. J Immunol 2008; 180:7287-93. PubMed
  • Taplin ME, Manola J, Oh WK, Kantoff PW, Bubley GJ, Smith M, Barb D, Mantzoros C, Gelmann EP, Balk SP. A phase II study of mifepristone (RU-486) in castration-resistant prostate cancer, with a correlative assessment of androgen-related hormones. BJU Int 2008; 101:1084-9. PubMed
  • Wang H, Leav I, Ibaragi S, Wegner M, Hu GF, Lu ML, Balk SP, Yuan X. SOX9 is expressed in human fetal prostate epithelium and enhances prostate cancer invasion. Cancer Res 2008; 68:1625-30. PubMed
  • Balk SP, Knudsen KE. AR, the cell cycle, and prostate cancer. Nucl Recept Signal 2008; 6:e001. PubMed
  • Barb D, Neuwirth A, Mantzoros CS, Balk SP. Adiponectin signals in prostate cancer cells through Akt to activate the mammalian target of rapamycin pathway. Endocr Relat Cancer 2007; 14:995-1005. PubMed
  • Jiang X, Borgesi RA, McKnight NC, Kaur R, Carpenter CL, Balk SP. Activation of nonreceptor tyrosine kinase Bmx/Etk mediated by phosphoinositide 3-kinase, epidermal growth factor receptor, and ErbB3 in prostate cancer cells. J Biol Chem 2007; 282:32689-98. PubMed
  • Hodgson MC, Astapova I, Hollenberg AN, Balk SP. Activity of androgen receptor antagonist bicalutamide in prostate cancer cells is independent of NCoR and SMRT corepressors. Cancer Res 2007; 67:8388-95. PubMed
  • Li H, Bubley GJ, Balk SP, Gaziano JM, Pollak M, Stampfer MJ, Ma J. Hypoxia-inducible factor-1alpha (HIF-1alpha) gene polymorphisms, circulating insulin-like growth factor binding protein (IGFBP)-3 levels and prostate cancer. Prostate 2007; 67:1354-61. PubMed
  • van der Vliet HJ, Koon HB, Atkins MB, Balk SP, Exley MA. Exploiting regulatory T-cell populations for the immunotherapy of cancer. J Immunother 2007; 30:591-5. PubMed
  • van Dervliet HJ, Koon HB, Yue SC, Uzunparmak B, Seery V, Gavin MA, Rudensky AY, Atkins MB, Balk SP, Exley MA. Effects of the administration of high-dose interleukin-2 on immunoregulatory cell subsets in patients with advanced melanoma and renal cell cancer. Clin Cancer Res 2007; 13:2100-8. PubMed
  • Cai C, Chen SY, Zheng Z, Omwancha J, Lin MF, Balk SP, Shemshedini L. Androgen regulation of soluble guanylyl cyclasealpha1 mediates prostate cancer cell proliferation. Oncogene 2006; 26:1606-15. PubMed
  • Masiello D, Mohi MG, McKnight NC, Smith B, Neel BG, Balk SP, Bubley GJ. Combining an mTOR Antagonist and Receptor Tyrosine Kinase Inhibitors for the Treatment of Prostate Cancer. Cancer Biol Ther 2007; 6:195-201. PubMed
  • Wang H, McKnight NC, Zhang T, Lu ML, Balk SP, Yuan X. SOX9 is expressed in normal prostate basal cells and regulates androgen receptor expression in prostate cancer cells. Cancer Res 2007; 67:528-36. PubMed
  • Reddy GK, Balk SP. Clinical utility of microarray-derived genetic signatures in predicting outcomes in prostate cancer. Clin Genitourin Cancer 2007; 5:187-9. PubMed
  • Chen S, Xu Y, Yuan X, Bubley GJ, Balk SP. Androgen receptor phosphorylation and stabilization in prostate cancer by cyclin-dependent kinase 1. Proc Natl Acad Sci U S A 2006; 103:15969-74. PubMed
  • van der Vliet HJ, Balk SP, Exley MA. Natural killer T cell-based cancer immunotherapy. Clin Cancer Res 2006; 12:5921-3. PubMed
  • Yuan X, Li T, Wang H, Zhang T, Barua M, Borgesi RA, Bubley GJ, Lu ML, Balk SP. Androgen receptor remains critical for cell-cycle progression in androgen-independent CWR22 prostate cancer cells. Am J Pathol 2006; 169:682-96. PubMed
  • Xu Y, Chen SY, Ross KN, Balk SP. Androgens induce prostate cancer cell proliferation through mammalian target of rapamycin activation and post-transcriptional increases in cyclin D proteins. Cancer Res 2006; 66:7783-92. PubMed
  • Ilyinskii PO, Wang R, Balk SP, Exley MA. CD1d mediates T-cell-dependent resistance to secondary infection with encephalomyocarditis virus (EMCV) in vitro and immune response to EMCV infection in vivo. J Virol 2006; 80:7146-58. PubMed
  • Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, Febbo PG, Balk SP. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res 2006; 66:2815-25. PubMed
  • Chen SY, Wulf G, Zhou XZ, Rubin MA, Lu KP, Balk SP. Activation of beta-catenin signaling in prostate cancer by peptidyl-prolyl isomerase Pin1-mediated abrogation of the androgen receptor-beta-catenin interaction. Mol Cell Biol 2006; 26:929-39. PubMed