DF/HCC Program Affiliation

Cancer Genetics
Prostate Cancer, Co-Leader

DF/HCC Associations

Member, Center Scientific Council

Research Abstract

Skeletal complications are a major cause of prostate cancer morbidity. Gonadal steroid deprivation, the mainstay of treatment for advanced prostate cancer, may contribute to the skeletal morbidity of prostate cancer by accelerating bone loss and increasing the rate of osteoporotic fractures. In addition, changes in the bone microenvironment that accompany gonadal steroid deprivation may promote the growth of skeletal metastases. The goal of my research is to understand and prevent the skeletal complications of prostate cancer. Current research efforts will determine the magnitude of bone loss in men with prostate cancer, evaluate the effectiveness of several treatment strategies, and investigate the mechanisms of treatment-related bone loss. Related research efforts include evaluation of the effects of gonadal steroid deprivation on body composition, including muscle size and strength.

Publications

• 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
  18399827
• Smith MR, Malkowicz SB, Chu F, Forrest J, Sieber P, Barnette KG, Rodriquez D, Steiner MS.Toremifene improves lipid profiles in men receiving androgen-deprivation therapy for prostate cancer: interim analysis of a multicenter phase III study.J Clin Oncol 2
  18398147
• Hirsh V, Major PP, Lipton A, Cook RJ, Langer CJ, Smith MR, Brown JE, Coleman RE.Zoledronic acid and survival in patients with metastatic bone disease from lung cancer and elevated markers of osteoclast activity.J Thorac Oncol 2008 Mar;3(3):228-36.
  18317064
• Smith MR, Lee H, Fallon MA, Nathan DM.Adipocytokines, obesity, and insulin resistance during combined androgen blockade for prostate cancer.Urology 2008 Feb;71(2):318-22.
  18308111
• Efstathiou JA, Bae K, Shipley WU, Hanks GE, Pilepich MV, Sandler HM, Smith MR.Cardiovascular Mortality and Duration of Androgen Deprivation for Locally Advanced Prostate Cancer: Analysis of RTOG 92-02.Eur Urol 2008 Jan 15.
  18243498
• Keating NL, O'Malley AJ, McNaughton-Collins M, Oh WK, Smith MR.Use of androgen deprivation therapy for metastatic prostate cancer in older men.BJU Int 2008 Jan 8.
  18190632
• Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, Ryan P, Balis UJ, Tompkins RG, Haber DA, Toner M.Isolation of rare circulating tumour cells in cancer patients by microchip technology.Nature 2
  18097410
• Pirl WF, Greer JA, Goode M, Smith MR.Prospective study of depression and fatigue in men with advanced prostate cancer receiving hormone therapy.Psychooncology 2007 Apr 18.
  17443645
• Michaelson MD, Kaufman DS, Lee H, McGovern FJ, Kantoff PW, Fallon MA, Finkelstein JS, Smith MR.Randomized controlled trial of annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer.J Clin Onc
  17369566
• Oh WK, Proctor K, Nakabayashi M, Evan C, Tormey LK, Daskivich T, Antràs L, Smith M, Neary MP, Duh MS.The risk of renal impairment in hormone-refractory prostate cancer patients with bone metastases treated with zoledronic acid.Cancer 2007 Mar 15;109(6):10
  17311345
• Smith MR.Obesity and sex steroids during gonadotropin-releasing hormone agonist treatment for prostate cancer.Clin Cancer Res 2007 Jan 1;13(1):241-5.
  17200361
• Smith MR.Treatment-related osteoporosis in men with prostate cancer.Clin Cancer Res 2006 Oct 15;12(20 Pt 2):6315s-6319s.
  17062721
• Lipton A, Berenson JR, Body JJ, Boyce BF, Bruland OS, Carducci MA, Cleeland CS, Clohisy DR, Coleman RE, Cook RJ, Guise TA, Pearse RN, Powles TJ, Rogers MJ, Roodman GD, Smith MR, Suva LJ, Vessella RL, Weilbaecher KN, King L.Advances in treating metastatic
  17062702
• Smith MR.Selective estrogen receptor modulators to prevent treatment-related osteoporosis.Rev Urol 2005;7 Suppl 3:S30-5.
  16985877
• Keating NL, O'Malley AJ, Smith MR.Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer.J Clin Oncol 2006 Sep 20;24(27):4448-56.
  16983113
• Michaelson MD, Kaufman DS, Kantoff P, Oh WK, Smith MR.Randomized phase II study of atrasentan alone or in combination with zoledronic acid in men with metastatic prostate cancer.Cancer 2006 Jun 27.
  16804927
• Smith MR, Manola J, Kaufman DS, Oh WK, Bubley GJ, Kantoff PW.Celecoxib versus placebo for men with prostate cancer and a rising serum prostate-specific antigen after radical prostatectomy and/or radiation therapy.J Clin Oncol 2006 Jun 20;24(18):2723-8.
  16782912
• Redfern CH, Guthrie TH, Bessudo A, Densmore JJ, Holman PR, Janakiraman N, Leonard JP, Levy RL, Just RG, Smith MR, Rosenfelt FP, Wiernik PH, Carter WD, Gold DP, Melink TJ, Gutheil JC, Bender JF.Phase II trial of idiotype vaccination in previously treated p
  16754937
• Cook RJ, Coleman R, Brown J, Lipton A, Major P, Hei YJ, Saad F, Smith MR.Markers of bone metabolism and survival in men with hormone-refractory metastatic prostate cancer.Clin Cancer Res 2006 Jun 1;12(11 Pt 1):3361-7.
  16740758
• Bevers TB, Anderson BO, Bonaccio E, Borgen PI, Buys S, Daly MB, Dempsey PJ, Farrar WB, Fleming I, Garber JE, Harris RE, Helvie M, Hoover S, Krontiras H, Shaw S, Singletary E, Sugg Skinner C, Smith ML, Tsangaris TN, Wiley EL, Williams C.Breast cancer scree
  16687096
• Smith MR.Markers of bone metabolism in prostate cancer.Cancer Treat Rev 2006;32 Suppl 1:23-6.
  16680835
• Smith MR, Joshi I, Jin F, Al-Saleem T.Murine model for mantle cell lymphoma.Leukemia 2006 May;20(5):891-3.
  16525491
• Zelenetz AD, Advani RH, Buadi F, Cabanillas F, Caligiuri MA, Czuczman MS, Damon LE, Fayad L, Flinn IW, Forero A, Glenn MJ, Gockerman JP, Gordon LI, Harris NL, Hoppe RT, Kaminski MS, Lacasce AS, Nademanee A, Porcu P, Press O, Prosnitz L, Smith MR, Sotomayo
  16507273
• Taneja SS, Smith MR, Dalton JT, Raghow S, Barnette G, Steiner M, Veverka KA.Toremifene--a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy.Expert Opin Investig Drugs 2006 Mar;15(3):293-305.
  16503765
• Smith MR.Therapy Insight: osteoporosis during hormone therapy for prostate cancer.Nat Clin Pract Urol 2005 Dec;2(12):608-15; quiz 628.
  16474548
• Smith MR, Lee H, Nathan DM.Insulin sensitivity during combined androgen blockade for prostate cancer.J Clin Endocrinol Metab 2006 Apr;91(4):1305-8.
  16434464
• Smith MR, Boyce SP, Moyneur E, Duh MS, Raut MK, Brandman J.Risk of clinical fractures after gonadotropin-releasing hormone agonist therapy for prostate cancer.J Urol 2006 Jan;175(1):136-9; discussion 139.
  16406890
• Michaelson MD, Smith MR.Bisphosphonates for treatment and prevention of bone metastases.J Clin Oncol 2005 Nov 10;23(32):8219-24.
  16278476
• Smith MR, Lee WC, Brandman J, Wang Q, Botteman M, Pashos CL.Gonadotropin-releasing hormone agonists and fracture risk: a claims-based cohort study of men with nonmetastatic prostate cancer.J Clin Oncol 2005 Nov 1;23(31):7897-903.
  16258089
• Lee H, McGovern K, Finkelstein JS, Smith MR.Changes in bone mineral density and body composition during initial and long-term gonadotropin-releasing hormone agonist treatment for prostate carcinoma.Cancer 2005 Oct 15;104(8):1633-7.
  16116596
• Smith MR, Nelson JB.Future therapies in hormone-refractory prostate cancer.Urology 2005 May;65(5 Suppl):9-16; discussion 17.
  15885273
• Smith MR, Kabbinavar F, Saad F, Hussain A, Gittelman MC, Bilhartz DL, Wynne C, Murray R, Zinner NR, Schulman C, Linnartz R, Zheng M, Goessl C, Hei YJ, Small EJ, Cook R, Higano CS.Natural history of rising serum prostate-specific antigen in men with castra
  15860850
• Oh WK, Hagmann E, Manola J, George DJ, Gilligan TD, Jacobson JO, Smith MR, Kaufman DS, Kantoff PW.A phase I study of estramustine, weekly docetaxel, and carboplatin chemotherapy in patients with hormone-refractory prostate cancer.Clin Cancer Res 2005 Jan
  15671557
• Michaelson MD, Smith MR, Talcott JA.Prostate cancer (metastatic).Clin Evid 2003 Dec(10):1012-22.
  15555135
• Oh WK, Kantoff PW, Weinberg V, Jones G, Rini BI, Derynck MK, Bok R, Smith MR, Bubley GJ, Rosen RT, DiPaola RS, Small EJ.Prospective, Multicenter, Randomized Phase II Trial of the Herbal Supplement, PC-SPES, and Diethylstilbestrol in Patients With Androgen
  15289492
• Smith MR, Goode M, Zietman AL, McGovern FJ, Lee H, Finkelstein JS.Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition.J Clin Oncol 2004 Jul 1;22(13):2546-53.
  15226323
• Michaelson MD, Marujo RM, Smith MR.Contribution of androgen deprivation therapy to elevated osteoclast activity in men with metastatic prostate cancer.Clin Cancer Res 2004 Apr 15;10(8):2705-8.
  15102674
• Oh WK, Manola J, Bittmann L, Brufsky A, Kaplan ID, Smith MR, Kaufman DS, Kantoff PW.Finasteride and flutamide therapy in patients with advanced prostate cancer: response to subsequent castration and long-term follow-up.Urology 2003 Jul;62(1):99-104.
  12837431
• Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S, Zinner N.Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer.J Urol 2003 Jun;169(6):2008-12.
  12771706
• Smith MR, Fallon MA, Goode MJ.Cross-sectional study of bone turnover during bicalutamide monotherapy for prostate cancer.Urology 2003 Jan;61(1):127-31.
  12559282
• Smith MR, Kaufman D, George D, Oh WK, Kazanis M, Manola J, Kantoff PW.Selective aromatase inhibition for patients with androgen-independent prostate carcinoma.Cancer 2002 Nov 1;95(9):1864-8.
  12404279
• Smith MR, Kantoff PW.Peroxisome proliferator-activated receptor gamma (PPargamma) as a novel target for prostate cancer.Invest New Drugs 2002 May;20(2):195-200.
  12099579
• Smith MR, Finkelstein JS, McGovern FJ, Zietman AL, Fallon MA, Schoenfeld DA, Kantoff PW.Changes in body composition during androgen deprivation therapy for prostate cancer.J Clin Endocrinol Metab 2002 Feb;87(2):599-603.
  11836291
• Smith MR, McGovern FJ, Zietman AL, Fallon MA, Hayden DL, Schoenfeld DA, Kantoff PW, Finkelstein JS.Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer.N Engl J Med 2001 Sep 27;345(13):948-55.
  11575286