Principal Investigator: Steven P. Balk, MD, PhD

About Steven P. Balk, MD, PhD

Dr. Balk's main objective has been to conduct disease focused integrated basic and translational research and to equip MD and/or PhD trainees to do the same. The initial focus of his lab was immunology, but in 1993 he initiated a major research effort in prostate cancer (PCa).

His lab developed methods to analyze advanced metastatic PCa through the use of bone marrow biopsies and showed that one mechanism for disease progression after androgen deprivation therapy was through mutations in the androgen receptor (AR). These mutations occur specifically in patients treated with an AR antagonist, flutamide, and are the result of strong selective pressure exerted by this drug. In subsequent studies his lab has further established a critical role for AR in PCa that relapses after androgen deprivation therapy, and identified mechanisms that mediate AR reactivation (including enhanced androgen synthesis by tumor cells). These results have led directly to successful clinical trials with translational as well as clinical endpoints. An additional current focus is mechanisms of progression from low grade to high grade prostate cancer, which will have an impact on management of low grade disease. In conjunction with these research efforts, he has directed the establishment of a prostate cancer tissue bank and correlative clinical database.

His teaching efforts have focused primarily on exposing clinical fellows to basic research and mentoring them in the conduct of translational and clinical research, and in training basic research PhDs. His major clinical contributions are currently in the expansion of our clinical database and tissue bank for PCa and in the design and execution of clinical trials.

Email Dr. Balk

Positions

Intern in Medicine, New England Deaconess Hospital, Boston, MA: 1983-1984
Resident in Medicine, New England Deaconess Hospital, Boston, MA: 1984-1985
Clinical Fellow in Medicine (Hematology/Oncology), Beth Israel Hospital, and Harvard Medical School, Boston, MA: 1985-1988
Research Fellow, Beth Israel Hospital, Dana Farber Cancer Institute, and Harvard Medical School Boston, MA: 1986-1988
Instructor in Medicine, Harvard Medical School, Boston, MA: 1988-1992
Staff Physician, Beth Israel Deaconess Medical Center, Boston, MA: 1988-present
Assistant Professor of Medicine, Harvard Medical School, Boston, MA: 1992-1998
American Society for Clinical Investigation, member: 1996-present
Associate Professor of Medicine, Harvard Medical School, Boston, MA: 1998-2010
Director, DNA Sequencing, quantitative RT-PCR, Laser Capture Microdissection Core Facilities, BIDMC: 2000-present
Assistant Director, BIDMC Training Grant in Cancer Biology: 2002-2006
Associate Editor, Journal of Immunology: 2002-2006
Director, BIDMC Training Grant in Cancer Biology: 2007-present
Association of American Physicians: 2010-present
Professor of Medicine, Harvard Medical School, Boston, MA: 2010-present
Senior Editor, Cancer Research: 2013-present

Education

BA: University of Pennsylvania: 1976
MD: Harvard-MIT Health Sciences and Technology Program: 1983
PhD: Harvard University (PhD, Cell & Develop. Biology): 1983

Licensure and Certification

Massachusetts Medical License: 1984
American Board of Internal Medicine: 1986

Major Committee Assignments

Hospital/Medical School:
Hematology-Oncology Fellowship Selection Committee, BIDMC: 1998-present
Steering Committee, Harvard Translational Immunology Center, Harvard
University: 2005
Harvard-MIT Health Sciences and Technology (HST) Admission Committee: 2007-present
PhD Program in Biological and Biomedical Sciences (BBS): 2007-present
Harvard Program in Human Biology and Translational Medicine (HBTM): 2007-present

National:
Biochemical Endocrinology Study Section ad hoc reviewer NIH: 1997
Prostate Cancer Study Section ad hoc reviewer DOD: 1999-2005
Biochemical Endocrinology Study Section ad hoc reviewer NIH: 1999
SEP: Sex Based Differences in Immunity ad hoc reviewer NIH: 2001
Immunological Sciences Study Section ad hoc reviewer NIH: 2001
Experimental Immunology Study Section ad hoc reviewer NIH: 2002
Biochemical Endocrinology Study Section ad hoc reviewer NIH: 2002
SEP: Radiation Study Section ad hoc reviewer NIH: 2002
SEP: Environmental Health Sciences ad hoc reviewer NIH: 2002
Immunological Sciences Study Section ad hoc reviewer NIH: 2003
SEP: Urology Research Centers ad hoc reviewer NIH: 2003
SEP: Urology Development of Cell… ad hoc reviewer NIH: 2003
Subcommittee C, Prostate Cancer Section ad hoc reviewer NIH: 2004
Transplantation, Tolerance, and Tumor ad hoc reviewer NIH
Immunology Study Section: 2004
Urologic and Kidney Development and ad hoc reviewer NIH
Genitourinary Diseases Study Section: 2004
Subcommittee E, Cancer Epidemiology, ad hoc reviewer NIH
Prevention, and Control: 2005
Prostate Cancer Study Section ad hoc reviewer DOD: 2005
Prostate Cancer Program ad hoc reviewer NCI-Canada: 2005
Transplantation, Tolerance, and Tumor ad hoc reviewer NIH
Immunology Study Section: 2006
Co-chair, Androgen Working Group, NCI-
Prostate SPORE program: 2007
Urologic and Kidney Development and ad hoc reviewer NIH
Genitourinary Diseases Study Section: 2007
Louisiana Board of Regents Research Grants ad hoc reviewer: 2007
NCI-F Manpower & Training Grants Study ad hoc reviewer NIH
Section: 2007
Tumor Microenvironment Study Section ad hoc reviewer NIH: 2008
Urologic and Kidney Development and ad hoc reviewer NIH
Genitourinary Diseases Study Section: 2008
NCI-F Manpower & Training Grants Study Section member NIH: 2008-2012
Department of Defense Prostate Cancer Research Program DOD Integration Panel: 2008-2009
Cancer Molecular Pathology Study Section ad hoc reviewer NIH: 2012

Awards and Honors

NCI, Physician Scientist Award: 1987
American Cancer Society Junior Faculty Research Award: 1992
Prostate Cancer Foundation Challenge Award: 2008 

Recent Publications  

Click here to go to full list in Pubmed. 

  1. ARv7 Represses Tumor-Suppressor Genes in Castration-Resistant Prostate Cancer.

    Cato L, de Tribolet-Hardy J, Lee I, Rottenberg JT, Coleman I, Melchers D, Houtman R, Xiao T, Li W, Uo T, Sun S, Kuznik NC, Göppert B, Ozgun F, van Royen ME, Houtsmuller AB, Vadhi R, Rao PK, Li L, Balk SP, Den RB, Trock BJ, Karnes RJ, Jenkins RB, Klein EA, Davicioni E, Gruhl FJ, Long HW, Liu XS, Cato ACB, Lack NA, Nelson PS, Plymate SR, Groner AC, Brown M.

    Cancer Cell. 2019 Feb 12. pii: S1535-6108(19)30042-X. doi: 10.1016/j.ccell.2019.01.008. [Epub ahead of print]

    PMID: 30773341

  2. Androgen receptor splice variant-7 expression emerges with castration resistance in prostate cancer.

    Sharp A, Coleman I, Yuan W, Sprenger C, Dolling D, Rodrigues DN, Russo JW, Figueiredo I, Bertan C, Seed G, Riisnaes R, Uo T, Neeb A, Welti J, Morrissey C, Carreira S, Luo J, Nelson PS, Balk SP, True LD, de Bono JS, Plymate SR.

    J Clin Invest. 2019 Jan 2;129(1):192-208. doi: 10.1172/JCI122819. Epub 2018 Nov 26.

    PMID: 30334814

  3. Characteristics of myeloproliferative neoplasms in patients exposed to ionizing radiation following the Chernobyl nuclear accident.

    Poluben L, Puligandla M, Neuberg D, Bryke CR, Hsu Y, Shumeiko O, Yuan X, Voznesensky O, Pihan G, Adam M, Fraenkel E, Rasnic R, Linial M, Klymenko S, Balk SP, Fraenkel PG.

    Am J Hematol. 2019 Jan;94(1):62-73. doi: 10.1002/ajh.25307. Epub 2018 Oct 31.

    PMID: 30295334

  4. Contribution of Adrenal Glands to Intratumor Androgens and Growth of Castration-Resistant Prostate Cancer.

    Mostaghel EA, Zhang A, Hernandez S, Marck BT, Zhang X, Tamae D, Biehl HE, Tretiakova M, Bartlett J, Burns J, Dumpit R, Ang L, Matsumoto AM, Penning TM, Balk SP, Morrissey C, Corey E, True LD, Nelson PS.

    Clin Cancer Res. 2019 Jan 1;25(1):426-439. doi: 10.1158/1078-0432.CCR-18-1431. Epub 2018 Sep 4.

    PMID: 30181386

  5. Downregulation of Dipeptidyl Peptidase 4 Accelerates Progression to Castration-Resistant Prostate Cancer.

    Russo JW, Gao C, Bhasin SS, Voznesensky OS, Calagua C, Arai S, Nelson PS, Montgomery B, Mostaghel EA, Corey E, Taplin ME, Ye H, Bhasin M, Balk SP.

    Cancer Res. 2018 Nov 15;78(22):6354-6362. doi: 10.1158/0008-5472.CAN-18-0687. Epub 2018 Sep 21.

    PMID: 30242112

  6. Phosphorylation of androgen receptor serine 81 is associated with its reactivation in castration-resistant prostate cancer.

    Russo JW, Liu X, Ye H, Calagua C, Chen S, Voznesensky O, Condulis J, Ma F, Taplin ME, Einstein DJ, Balk SP, Chen S.

    Cancer Lett. 2018 Dec 1;438:97-104. doi: 10.1016/j.canlet.2018.09.014. Epub 2018 Sep 11.

    PMID: 30217568

  7. Tyrosine Kinase Inhibitors Increase MCL1 Degradation and in Combination with BCLXL/BCL2 Inhibitors Drive Prostate Cancer Apoptosis.

    Arai S, Jonas O, Whitman MA, Corey E, Balk SP, Chen S.

    Clin Cancer Res. 2018 Nov 1;24(21):5458-5470. doi: 10.1158/1078-0432.CCR-18-0549. Epub 2018 Jul 18.

    PMID: 30021909

  8. BMX-Mediated Regulation of Multiple Tyrosine Kinases Contributes to Castration Resistance in Prostate Cancer.

    Chen S, Cai C, Sowalsky AG, Ye H, Ma F, Yuan X, Simon NI, Gray NS, Balk SP.

    Cancer Res. 2018 Sep 15;78(18):5203-5215. doi: 10.1158/0008-5472.CAN-17-3615. Epub 2018 Jul 16.

    PMID: 30012673

  9. Neoadjuvant-Intensive Androgen Deprivation Therapy Selects for Prostate Tumor Foci with Diverse Subclonal Oncogenic Alterations.

    Sowalsky AG, Ye H, Bhasin M, Van Allen EM, Loda M, Lis RT, Montaser-Kouhsari L, Calagua C, Ma F, Russo JW, Schaefer RJ, Voznesensky OS, Zhang Z, Bubley GJ, Montgomery B, Mostaghel EA, Nelson PS, Taplin ME, Balk SP.

    Cancer Res. 2018 Aug 15;78(16):4716-4730. doi: 10.1158/0008-5472.CAN-18-0610. Epub 2018 Jun 19.

    PMID: 29921690

  10. Isolation and Functional Use of Human NKT Cells.

    Exley MA, Wilson SB, Balk SP.

    Curr Protoc Immunol. 2017 Nov 1;119:14.11.1-14.11.20. doi: 10.1002/cpim.33.

    PMID: 29091262

  11. Expression of PD-L1 in Hormone-naïve and Treated Prostate Cancer Patients Receiving Neoadjuvant Abiraterone Acetate plus Prednisone and Leuprolide.

    Calagua C, Russo J, Sun Y, Schaefer R, Lis R, Zhang Z, Mahoney K, Bubley GJ, Loda M, Taplin ME, Balk SP, Ye H.

    Clin Cancer Res. 2017 Nov 15;23(22):6812-6822. doi: 10.1158/1078-0432.CCR-17-0807. Epub 2017 Sep 11.

    PMID: 28893901

  12. Testicular vs adrenal sources of hydroxy-androgens in prostate cancer.

    Zang T, Taplin ME, Tamae D, Xie W, Mesaros C, Zhang Z, Bubley G, Montgomery B, Balk SP, Mostaghel EA, Blair IA, Penning TM.

    Endocr Relat Cancer. 2017 Aug;24(8):393-404. doi: 10.1530/ERC-17-0107. Epub 2017 Jun 29.

    PMID: 28663228

  13. Association Between Androgen Receptor Splice Variants and Prostate Cancer Resistance to Abiraterone and Enzalutamide.

    Bubley GJ, Balk SP.

    J Clin Oncol. 2017 Jul 1;35(19):2103-2105. doi: 10.1200/JCO.2017.72.8808. Epub 2017 Apr 17. No abstract available.

    PMID: 28414609

  14. Association of Tissue Abiraterone Levels and SLCO Genotype with Intraprostatic Steroids and Pathologic Response in Men with High-Risk Localized Prostate Cancer.

    Mostaghel EA, Cho E, Zhang A, Alyamani M, Kaipainen A, Green S, Marck BT, Sharifi N, Wright JL, Gulati R, True LD, Loda M, Matsumoto AM, Tamae D, Penning TN, Balk SP, Kantoff PW, Nelson PS, Taplin ME, Montgomery RB.

    Clin Cancer Res. 2017 Aug 15;23(16):4592-4601. doi: 10.1158/1078-0432.CCR-16-2245. Epub 2017 Apr 7.

    PMID: 28389510

  15. Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity.

    Patnaik A, Swanson KD, Csizmadia E, Solanki A, Landon-Brace N, Gehring MP, Helenius K, Olson BM, Pyzer AR, Wang LC, Elemento O, Novak J, Thornley TB, Asara JM, Montaser L, Timmons JJ, Morgan TM, Wang Y, Levantini E, Clohessy JG, Kelly K, Pandolfi PP, Rosenblatt JM, Avigan DE, Ye H, Karp JM, Signoretti S, Balk SP, Cantley LC.

    Cancer Discov. 2017 Jul;7(7):750-765. doi: 10.1158/2159-8290.CD-16-0778. Epub 2017 Mar 8.

  16. Adoptive Transfer of Invariant NKT Cells as Immunotherapy for Advanced Melanoma: A Phase I Clinical Trial.

    Exley MA, Friedlander P, Alatrakchi N, Vriend L, Yue S, Sasada T, Zeng W, Mizukami Y, Clark J, Nemer D, LeClair K, Canning C, Daley H, Dranoff G, Giobbie-Hurder A, Hodi FS, Ritz J, Balk SP.

    Clin Cancer Res. 2017 Jul 15;23(14):3510-3519. doi: 10.1158/1078-0432.CCR-16-0600. Epub 2017 Feb 13.

    PMID: 28193627

  17. Neoadjuvant Enzalutamide Prior to Prostatectomy.

    Montgomery B, Tretiakova MS, Joshua AM, Gleave ME, Fleshner N, Bubley GJ, Mostaghel EA, Chi KN, Lin DW, Sanda M, Novotny W, Wu K, Kantoff PW, Marck BT, Plymate S, Balk SP, Nelson PS, Matsumoto AM, Lis RT, Kibel A, Haas GP, Krivoshik A, Hannah A, Taplin ME.

    Clin Cancer Res. 2017 May 1;23(9):2169-2176. doi: 10.1158/1078-0432.CCR-16-1357. Epub 2016 Nov 9.

    PMID: 28151719

  18. Gleason Score 7 Prostate Cancers Emerge through Branched Evolution of Clonal Gleason Pattern 3 and 4.

    Sowalsky AG, Kissick HT, Gerrin SJ, Schaefer RJ, Xia Z, Russo JW, Arredouani MS, Bubley GJ, Sanda MG, Li W, Ye H, Balk SP.

    Clin Cancer Res. 2017 Jul 15;23(14):3823-3833. doi: 10.1158/1078-0432.CCR-16-2414. Epub 2017 Jan 24.

    PMID: 28119368

  19. Positive feedback loop mediated by protein phosphatase 1α mobilization of P-TEFb and basal CDK1 drives androgen receptor in prostate cancer.

    Liu X, Gao Y, Ye H, Gerrin S, Ma F, Wu Y, Zhang T, Russo J, Cai C, Yuan X, Liu J, Chen S, Balk SP.

    Nucleic Acids Res. 2017 Apr 20;45(7):3738-3751. doi: 10.1093/nar/gkw1291.

    PMID: 28062857

Book Chapters, Letters, and Reviews

24. Yuan, X., Cai, C., Chen, S., Chen, S., Yu, Z. and Balk, S.P. (2013). Androgen receptor functions in castration-resistant prostate cancer and mechanisms of resistance to new agents targeting the androgen axis. Oncogene, Jun 10.
23. Cai, C., and Balk, S.P. (2011). Intratumoral androgen biosynthesis in prostate cancer pathogenesis and response to therapy. Endocr Relat Cancer 18, R175-182.
22. Exley, M.A., Lynch, L., Varghese, B., Nowak, M., Alatrakchi, N., and Balk, S.P. (2011). Developing understanding of the roles of CD1d-restricted T cell subsets in cancer: Reversing tumor-induced defects. Clin Immunol 140, 184-195.
21. Shen,H.C. and Balk,S.P. (2009). Development of androgen receptor antagonists with promising activity in castration-resistant prostate cancer. Cancer Cell 15, 461-463.
20. Yuan X, Balk SP. Mechanisms mediating androgen receptor reactivation after castration. Urol Oncol 2009;27:36-41.
19. Balk,S.P. and Knudsen,K.E. (2008). AR, the cell cycle, and prostate cancer. Nucl. Recept. Signal. 6, e001
18. van der Vliet,H.J., Koon,H.B., Atkins,M.B., Balk,S.P., and Exley,M.A. (2007). Exploiting regulatory T-cell populations for the immunotherapy of cancer. J. Immunother. 30, 591-595.
17. Probert,C.S., Saubermann,L.J., Balk,S., and Blumberg,R.S. (2007). Repertoire of the alpha beta T-cell receptor in the intestine. Immunol. Rev. 215, 215-225.
16. van der Vliet,H.J., Balk,S.P., and Exley,M.A. (2006). Natural killer T cell-based cancer immunotherapy. Clin. Cancer Res. 12, 5921-5923.
15, Reddy,G.K. and Balk,S.P. (2006). Clinical utility of microarray-derived genetic signatures in predicting outcomes in prostate cancer. Clin. Genitourin. Cancer 5, 187-189.
14. Ko,Y.J. and Balk,S.P. (2004). Targeting steroid hormone receptor pathways in the treatment of hormone dependent cancers. Curr. Pharm. Biotechnol. 5, 459-470.
13. Taplin,M.E. and Balk,S.P. (2004). Androgen receptor: a key molecule in the progression of prostate cancer to hormone independence. J. Cell Biochem. 91, 483-490.
12. Cheng,S. and Balk,S.P. (2003). Steroid hormone receptor signaling in cancer. Cancer Treat. Res. 115, 293-318.
11. Balk,S.P., Ko,Y.J., and Bubley,G.J. (2003). Biology of prostate-specific antigen. J. Clin. Oncol. 21, 383-391.
10. Carroll,P.R., Kantoff,P.W., Balk,S.P., Brown,M.A., D'amico,A.V., George,D.J., Grossfeld,G.D., Johnson,C.S., Kelly,W.K., Klotz,L., Lee,W.R., Lubeck,D.P., Mcleod,D.G., Oh,W.K., Pollack,A., Sartor,O., Smith,M.R., and Hart,C. (2002). Overview consensus statement. Newer approaches to androgen deprivation therapy in prostate cancer. Urology 60, 1-6.
9. Balk,S.P. (2002). Androgen receptor as a target in androgen-independent prostate cancer. Urology 60, 132-138.
8. Blumberg,R.S., Colgan,S.P., and Balk,S.P. (1997). CD1d: outside-in antigen presentation in the intestinal epithelium? Clin. Exp. Immunol. 109, 223-225.
7. Bubley,G.J. and Balk,S.P. (1996). Treatment of Androgen-Independent Prostate Cancer. Oncologist. 1, 30-35.
6. Bubley,G.J. and Balk,S.P. (1996). Treatment of metastatic prostate cancer. Lessons from the androgen receptor. Hematol. Oncol. Clin. North Am. 10, 713-725.
5. Blumberg,R.S., Gerdes,D., Chott,A., Porcelli,S.A., and Balk,S.P. (1995). Structure and function of the CD1 family of MHC-like cell surface proteins. Immunol. Rev. 147, 5-29.
4. Balk,S. (1995). MHC evolution. Nature 374, 505-506.
3. Blumberg,R.S. and Balk,S.P. (1994). Intraepithelial lymphocytes and their recognition of non-classical MHC molecules. Int. Rev. Immunol. 11, 15-30.
2. Balk,S. and Terhorst,C. (1989). Relationship between the T-cell receptor-T3 complex and Thy-1. Immunol. Ser. 45, 411-416.
1. Bleicher,P.A. and Balk,S.P. (1988). T-cell receptor gene rearrangements. Progress and promise. Arch. Dermatol. 124, 359-363.

Patents

PCT/US2011/064852 filed Dec. 14, 2011, Androgen Receptor Antagonists for Prostate Cancer Therapy

Link to Dr. Balk's Harvard Catalyst Page