Novel Computational Method Deprivation in Patients with Prostate Cancer Identified by a Mechanisms of Resistance to Intermittent Androgen

Abstract For progressive prostatecancer, intermittent androgen deprivation (IAD) is oneof themostcommonandeffectivetreatments.Althoughthistreatmentisusuallyinitiallyeffectiveatregressingtumors,mostpatientseventually develop castration-resistant prostate cancer (CRPC), for which there is no effective treatmentandisgenerallyfatal.AlthoughseveralbiologicmechanismsleadingtoCRPCdevelopmentandtheirrelativefrequencies have been identified, it is difficult to determine which mechanisms of resistance are developingin a given patient. Personalized therapy that identifies and targets specific mechanisms of resistancedeveloping in individual patients is likely one of the most promising methods of future cancer therapy.Prostate-specific antigen (PSA) is a biomarker for monitoring tumor progression. We incorporated a celldeath rate (CDR) function into a previous dynamical PSA model that was highly accurate atfitting clinicalPSA data for 7 patients. The mechanism of action of IAD is largely induction of apoptosis, and eachmechanism of resistance varies in its CDR dynamics. Thus, we analyze the CDR levels and their time-dependentoscillationstoidentifymechanismsofresistancetoIADdevelopinginindividualpatients.CancerRes; 74(14); 1–11. 2014 AACR.

[1]  N. Mitsiades.  A road map to comprehensive androgen receptor axis targeting for castration-resistant prostate cancer. , 2013, Cancer research.

[2]  Jason K. Wang,et al.  Molecular pathology of prostate cancer revealed by next-generation sequencing: opportunities for genome-based personalized therapy , 2013, Current opinion in urology.

[3]  Donna L Berry,et al.  Intermittent versus continuous androgen deprivation in prostate cancer. , 2013, The New England journal of medicine.

[4]  Long-Cheng Li,et al.  Adaptation and clonal selection models of castration‐resistant prostate cancer: Current perspective , 2013, International journal of urology : official journal of the Japanese Urological Association.

[5]  A. Goldstein,et al.  Adaptation or selection—mechanisms of castration-resistant prostate cancer , 2013, Nature Reviews Urology.

[6]  Kurt Miller,et al.  Increased survival with enzalutamide in prostate cancer after chemotherapy. , 2012, The New England journal of medicine.

[7]  Tapio Visakorpi,et al.  Androgen receptor (AR) aberrations in castration-resistant prostate cancer , 2012, Molecular and Cellular Endocrinology.

[8]  Kazuyuki Aihara,et al.  Quantitative mathematical modeling of PSA dynamics of prostate cancer patients treated with intermittent androgen suppression. , 2012, Journal of molecular cell biology.

[9]  Travis Portz,et al.  A clinical data validated mathematical model of prostate cancer growth under intermittent androgen suppression therapy , 2012 .

[10]  P. Nelson.  Molecular states underlying androgen receptor activation: a framework for therapeutics targeting androgen signaling in prostate cancer. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  G. Sonpavde,et al.  Epigenetics in Prostate Cancer , 2011, Prostate cancer.

[12]  D. Tindall,et al.  Alternatively spliced androgen receptor variants. , 2011, Endocrine-related cancer.

[13]  Arturo Molina,et al.  Abiraterone and increased survival in metastatic prostate cancer. , 2011, The New England journal of medicine.

[14]  P. Nelson,et al.  Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. , 2010, The Journal of clinical investigation.

[15]  Kazuyuki Aihara,et al.  Development of a mathematical model that predicts the outcome of hormone therapy for prostate cancer. , 2010, Journal of theoretical biology.

[16]  S. Goel,et al.  LHRH agonists for adjuvant therapy of early breast cancer in premenopausal women. , 2009, The Cochrane database of systematic reviews.

[17]  D. Dearnaley,et al.  Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. , 2009, Cancer research.

[18]  Oscar Lin,et al.  Fluorescence In situ Hybridization Analysis of Circulating Tumor Cells in Metastatic Prostate Cancer , 2009, Clinical Cancer Research.

[19]  C. Bevan,et al.  The Role of Androgen Receptor Mutations in Prostate Cancer Progression , 2009, Current genomics.

[20]  E. Barret,et al.  A 16-year clinical experience with intermittent androgen deprivation for prostate cancer: oncological results , 2009, World Journal of Urology.

[21]  Y. Vergouwe,et al.  Validation, updating and impact of clinical prediction rules: a review. , 2008, Journal of clinical epidemiology.

[22]  Gouhei Tanaka,et al.  A Mathematical Model of Intermittent Androgen Suppression for Prostate Cancer , 2008, J. Nonlinear Sci..

[23]  N. Bruchovsky,et al.  Quality of life, morbidity, and mortality results of a prospective phase II study of intermittent androgen suppression for men with evidence of prostate-specific antigen relapse after radiation therapy for locally advanced prostate cancer. , 2008, Clinical genitourinary cancer.

[24]  J Cuzick,et al.  Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials , 2007, The Lancet.

[25]  Trachette L. Jackson,et al.  A mathematical investigation of the multiple pathways to recurrent prostate cancer: comparison with experimental data. , 2004, Neoplasia.

[26]  W. Gerald,et al.  Targeting the androgen receptor: improving outcomes for castration-resistant prostate cancer. , 2004, Endocrine-related cancer.

[27]  Mohammad H. Rashid,et al.  Intermittent androgen deprivation therapy for prostate cancer. , 2004, The oncologist.

[28]  D. Feldman,et al.  The development of androgen-independent prostate cancer , 2001, Nature Reviews Cancer.

[29]  T C Gasser,et al.  Survey of gene amplifications during prostate cancer progression by high-throughout fluorescence in situ hybridization on tissue microarrays. , 1999, Cancer research.

[30]  Jeffrey C. Lagarias,et al.  Convergence Properties of the Nelder-Mead Simplex Method in Low Dimensions , 1998, SIAM J. Optim..

[31]  J. Isaacs,et al.  Role of programmed (apoptotic) cell death during the progression and therapy for prostate cancer , 1996, The Prostate.

[32]  G. Bubley,et al.  Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. , 1995, The New England journal of medicine.

[33]  R W Veltri,et al.  Implication of cell kinetic changes during the progression of human prostatic cancer. , 1995, Clinical cancer research : an official journal of the American Association for Cancer Research.

[34]  S. Goldenberg,et al.  Effects of intermittent androgen suppression on androgen‐dependent tumors. Apoptosis and serum prostate‐specific antigen , 1993, Cancer.

[35]  M. Droop.  SOME THOUGHTS ON NUTRIENT LIMITATION IN ALGAE 1 , 1973 .

[36]  J. Salk.  Clonal evolution in cancer , 2010 .

[37]  M. Stockler,et al.  Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer : a meta-analysis of individual patient data from randomised adjuvant trials. Commentary , 2007 .

[38]  E. Latulippe,et al.  Gene expression analysis of human prostate carcinoma during hormonal therapy identifies androgen-responsive genes and mechanisms of therapy resistance. , 2004, The American journal of pathology.

[39]  R. Vessella,et al.  Molecular determinants of resistance to antiandrogen therapy , 2004, Nature Medicine.

[40]  N. Bruchovsky,et al.  [Intermittent androgen deprivation]. , 2000, Der Urologe. Ausg. A.

[41]  J. Trapman,et al.  The androgen receptor in prostate cancer. , 1996, Pathology, research and practice.