Skip to main content
Erschienen in: Clinical & Experimental Metastasis 8/2014

01.12.2014 | Review

Improving treatment strategies for patients with metastatic castrate resistant prostate cancer through personalized computational modeling

verfasst von: Jill Gallaher, Leah M. Cook, Shilpa Gupta, Arturo Araujo, Jasreman Dhillon, Jong Y. Park, Jacob G. Scott, Julio Pow-Sang, David Basanta, Conor C. Lynch

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 8/2014

Einloggen, um Zugang zu erhalten

Abstract

Metastatic castrate resistant prostate cancer (mCRPC) is responsible for the majority of prostate cancer deaths with the median survival after diagnosis being 2 years. The metastatic lesions often arise in the skeleton, and current treatment options are primarily palliative. Using guidelines set forth by the National Comprehensive Cancer Network (NCCN), the medical oncologist has a number of choices available to treat the metastases. However, the sequence of those treatments is largely dependent on the patient history, treatment response and preferences. We posit that the utilization of personalized computational models and treatment optimization algorithms based on patient specific parameters could significantly enhance the oncologist’s ability to choose an optimized sequence of available therapies to maximize overall survival. In this perspective, we used an integrated team approach involving clinicians, researchers, and mathematicians, to generate an example of how computational models and genetic algorithms can be utilized to predict the response of heterogeneous mCRPCs in bone to varying sequences of standard and targeted therapies. The refinement and evolution of these powerful models will be critical for extending the overall survival of men diagnosed with mCRPC.
Literatur
2.
Zurück zum Zitat Mohler J et al (2010) NCCN clinical practice guidelines in oncology: prostate cancer. J Nat Compr Canc Netw 8(2):162–200 Mohler J et al (2010) NCCN clinical practice guidelines in oncology: prostate cancer. J Nat Compr Canc Netw 8(2):162–200
3.
Zurück zum Zitat Trewartha D, Carter K (2013) Advances in prostate cancer treatment. Nat Rev Drug Discov 12(11):823–824 Trewartha D, Carter K (2013) Advances in prostate cancer treatment. Nat Rev Drug Discov 12(11):823–824
4.
Zurück zum Zitat Floc’h N et al (2012) Dual targeting of the Akt/mTOR signaling pathway inhibits castration-resistant prostate cancer in a genetically engineered mouse model. Cancer Res 72(17):4483–4493 Floc’h N et al (2012) Dual targeting of the Akt/mTOR signaling pathway inhibits castration-resistant prostate cancer in a genetically engineered mouse model. Cancer Res 72(17):4483–4493
5.
Zurück zum Zitat Tam L et al (2007) Expression levels of the JAK/STAT pathway in the transition from hormone-sensitive to hormone-refractory prostate cancer. Br J Cancer 97(3):378–383 Tam L et al (2007) Expression levels of the JAK/STAT pathway in the transition from hormone-sensitive to hormone-refractory prostate cancer. Br J Cancer 97(3):378–383
6.
Zurück zum Zitat Kroon P et al (2013) JAK-STAT blockade inhibits tumor initiation and clonogenic recovery of prostate cancer stem-like cells. Cancer Res 73(16):5288–5298 Kroon P et al (2013) JAK-STAT blockade inhibits tumor initiation and clonogenic recovery of prostate cancer stem-like cells. Cancer Res 73(16):5288–5298
7.
Zurück zum Zitat Drake JM et al (2013) Metastatic castration-resistant prostate cancer reveals intrapatient similarity and interpatient heterogeneity of therapeutic kinase targets. Proc Nat Acad Sci USA 110(49):E4762–E4769 Drake JM et al (2013) Metastatic castration-resistant prostate cancer reveals intrapatient similarity and interpatient heterogeneity of therapeutic kinase targets. Proc Nat Acad Sci USA 110(49):E4762–E4769
10.
Zurück zum Zitat Smaletz O et al (2002) Nomogram for overall survival of patients with progressive metastatic prostate cancer after castration. J Clin Oncol (official journal of the American Society of Clinical Oncology) 20(19):3972–3982 Smaletz O et al (2002) Nomogram for overall survival of patients with progressive metastatic prostate cancer after castration. J Clin Oncol (official journal of the American Society of Clinical Oncology) 20(19):3972–3982
11.
Zurück zum Zitat Wang JZ et al (2010) A generalized linear-quadratic model for radiosurgery, stereotactic body radiation therapy, and high-dose rate brachytherapy. Sci Transl Med 2(39):39ra48 Wang JZ et al (2010) A generalized linear-quadratic model for radiosurgery, stereotactic body radiation therapy, and high-dose rate brachytherapy. Sci Transl Med 2(39):39ra48
12.
Zurück zum Zitat Leder K et al (2014) Mathematical modeling of PDGF-driven glioblastoma reveals optimized radiation dosing schedules. Cell 156(3):603–616 Leder K et al (2014) Mathematical modeling of PDGF-driven glioblastoma reveals optimized radiation dosing schedules. Cell 156(3):603–616
13.
Zurück zum Zitat Ross DM et al (2013) Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood 122(4):515–522 Ross DM et al (2013) Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood 122(4):515–522
14.
Zurück zum Zitat Morken JD et al (2014) Mechanisms of resistance to intermittent androgen deprivation in patients with prostate cancer identified by a novel computational method. Cancer Res 74(14):3673–3683 Morken JD et al (2014) Mechanisms of resistance to intermittent androgen deprivation in patients with prostate cancer identified by a novel computational method. Cancer Res 74(14):3673–3683
15.
Zurück zum Zitat Zhao B et al (2014) Addressing genetic tumor heterogeneity through computationally predictive combination therapy. Cancer Discov 4(2):166–174 Zhao B et al (2014) Addressing genetic tumor heterogeneity through computationally predictive combination therapy. Cancer Discov 4(2):166–174
16.
Zurück zum Zitat Rockne R et al (2010) Predicting the efficacy of radiotherapy in individual glioblastoma patients in vivo: a mathematical modeling approach. Phys Med Biol 55(12):3271–3285 Rockne R et al (2010) Predicting the efficacy of radiotherapy in individual glioblastoma patients in vivo: a mathematical modeling approach. Phys Med Biol 55(12):3271–3285
17.
Zurück zum Zitat Mundy GR (2002) Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2(8):584–593 Mundy GR (2002) Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2(8):584–593
18.
Zurück zum Zitat Cheng L et al (2004) Androgen withdrawal inhibits tumor growth and is associated with decrease in angiogenesis and VEGF expression in androgen-independent CWR22Rv1 human prostate cancer model. Anticancer Res 24(4):2135–2140 Cheng L et al (2004) Androgen withdrawal inhibits tumor growth and is associated with decrease in angiogenesis and VEGF expression in androgen-independent CWR22Rv1 human prostate cancer model. Anticancer Res 24(4):2135–2140
19.
Zurück zum Zitat Costelloe CM et al (2010) Cancer response criteria and bone metastases: RECIST 1.1. MDA PERCIST J Cancer 1:80–92CrossRef Costelloe CM et al (2010) Cancer response criteria and bone metastases: RECIST 1.1. MDA PERCIST J Cancer 1:80–92CrossRef
20.
Zurück zum Zitat Bianconi E et al (2013) An estimation of the number of cells in the human body. Ann Hum Biol 40(6):463–471 Bianconi E et al (2013) An estimation of the number of cells in the human body. Ann Hum Biol 40(6):463–471
21.
Zurück zum Zitat Blaszczyk N et al (2004) Osteoblast-derived factors induce androgen-independent proliferation and expression of prostate-specific antigen in human prostate cancer cells. Clin Cancer Res 10(5):1860–1869 Blaszczyk N et al (2004) Osteoblast-derived factors induce androgen-independent proliferation and expression of prostate-specific antigen in human prostate cancer cells. Clin Cancer Res 10(5):1860–1869
22.
Zurück zum Zitat Dagvadorj A et al (2008) Transcription factor signal transducer and activator of transcription 5 promotes growth of human prostate cancer cells in vivo. Clin Cancer Res 14(5):1317–1324 Dagvadorj A et al (2008) Transcription factor signal transducer and activator of transcription 5 promotes growth of human prostate cancer cells in vivo. Clin Cancer Res 14(5):1317–1324
23.
Zurück zum Zitat Agarwal C et al (2007) Silibinin inhibits constitutive activation of Stat3, and causes caspase activation and apoptotic death of human prostate carcinoma DU145 cells. Carcinogenesis 28(7):1463–1470 Agarwal C et al (2007) Silibinin inhibits constitutive activation of Stat3, and causes caspase activation and apoptotic death of human prostate carcinoma DU145 cells. Carcinogenesis 28(7):1463–1470
24.
Zurück zum Zitat Mostaghel EA et al (2011) Resistance to CYP17A1 inhibition with abiraterone in castration-resistant prostate cancer: induction of steroidogenesis and androgen receptor splice variants. Clin Cancer Res 17(18):5913–5925 Mostaghel EA et al (2011) Resistance to CYP17A1 inhibition with abiraterone in castration-resistant prostate cancer: induction of steroidogenesis and androgen receptor splice variants. Clin Cancer Res 17(18):5913–5925
25.
Zurück zum Zitat Dahlman KB et al (2012) Modulators of prostate cancer cell proliferation and viability identified by short-hairpin RNA library screening. PLoS ONE 7(4):e34414 Dahlman KB et al (2012) Modulators of prostate cancer cell proliferation and viability identified by short-hairpin RNA library screening. PLoS ONE 7(4):e34414
27.
Zurück zum Zitat Mukherjee A, Rotwein P (2009) Akt promotes BMP2-mediated osteoblast differentiation and bone development. J Cell Sci 122(Pt 5):716–726 Mukherjee A, Rotwein P (2009) Akt promotes BMP2-mediated osteoblast differentiation and bone development. J Cell Sci 122(Pt 5):716–726
28.
Zurück zum Zitat Gerland K et al (2000) Activation of the Jak/Stat signal transduction pathway in GH-treated rat osteoblast-like cells in culture. Mol Cell Endocrinol 168(1–2):1–9 Gerland K et al (2000) Activation of the Jak/Stat signal transduction pathway in GH-treated rat osteoblast-like cells in culture. Mol Cell Endocrinol 168(1–2):1–9
29.
Zurück zum Zitat Kostenuik PJ et al (2009) Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res 24(2):182–195 Kostenuik PJ et al (2009) Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res 24(2):182–195
30.
Zurück zum Zitat O’Donnell A et al (2004) Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br J Cancer 90(12):2317–2325 O’Donnell A et al (2004) Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br J Cancer 90(12):2317–2325
31.
Zurück zum Zitat McCall J (2005) Genetic algorithms for modelling and optimisation. J Comput Appl Math 184(1):205–222 McCall J (2005) Genetic algorithms for modelling and optimisation. J Comput Appl Math 184(1):205–222
32.
Zurück zum Zitat Bentley PJ (1999) Evolutionary design by computers. Morgan Kaufmann, San Francisco, USA Bentley PJ (1999) Evolutionary design by computers. Morgan Kaufmann, San Francisco, USA
33.
Zurück zum Zitat Brown JE, Coleman RE (2012) Denosumab in patients with cancer-a surgical strike against the osteoclast. Nat Rev Clin Oncol 9(2):110–118 Brown JE, Coleman RE (2012) Denosumab in patients with cancer-a surgical strike against the osteoclast. Nat Rev Clin Oncol 9(2):110–118
34.
Zurück zum Zitat Pal SK, Stein CA, Sartor O (2013) Enzalutamide for the treatment of prostate cancer. Expert Opin Pharmacol 14(5):679–685 Pal SK, Stein CA, Sartor O (2013) Enzalutamide for the treatment of prostate cancer. Expert Opin Pharmacol 14(5):679–685
35.
Zurück zum Zitat Kantoff PW, Mohler JL (2013) New developments in the management of prostate cancer. J Nat Compr Canc Netw 11(5 suppl):653–657 Kantoff PW, Mohler JL (2013) New developments in the management of prostate cancer. J Nat Compr Canc Netw 11(5 suppl):653–657
36.
Zurück zum Zitat Araujo A et al (2014) An integrated computational model of the bone microenvironment in bone-metastatic prostate cancer. Cancer Res 74(9):2391–2401 Araujo A et al (2014) An integrated computational model of the bone microenvironment in bone-metastatic prostate cancer. Cancer Res 74(9):2391–2401
37.
Zurück zum Zitat Sweeney C et al (2014) Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): An ECOG-led phase III randomized trial. J Clin Oncol 32:5s (suppl; abstr LBA2) Sweeney C et al (2014) Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): An ECOG-led phase III randomized trial. J Clin Oncol 32:5s (suppl; abstr LBA2)
38.
Zurück zum Zitat Sharma M, Chuang WW, Sun Z (2002) Phosphatidylinositol 3-kinase/Akt stimulates androgen pathway through GSK3beta inhibition and nuclear beta-catenin accumulation. J Biol Chem 277(34):30935–30941 Sharma M, Chuang WW, Sun Z (2002) Phosphatidylinositol 3-kinase/Akt stimulates androgen pathway through GSK3beta inhibition and nuclear beta-catenin accumulation. J Biol Chem 277(34):30935–30941
39.
Zurück zum Zitat Parfitt AM et al (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2(6):595–610 Parfitt AM et al (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2(6):595–610
40.
Zurück zum Zitat Nishiyama T (2014) Serum testosterone levels after medical or surgical androgen deprivation: a comprehensive review of the literature. Urol Oncol 32(1):38.e17–38.e28 Nishiyama T (2014) Serum testosterone levels after medical or surgical androgen deprivation: a comprehensive review of the literature. Urol Oncol 32(1):38.e17–38.e28
41.
Zurück zum Zitat Dahut WL et al (2004) Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer. J Clin Oncol 22(13):2532–2539 Dahut WL et al (2004) Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer. J Clin Oncol 22(13):2532–2539
Metadaten
Titel
Improving treatment strategies for patients with metastatic castrate resistant prostate cancer through personalized computational modeling
verfasst von
Jill Gallaher
Leah M. Cook
Shilpa Gupta
Arturo Araujo
Jasreman Dhillon
Jong Y. Park
Jacob G. Scott
Julio Pow-Sang
David Basanta
Conor C. Lynch
Publikationsdatum
01.12.2014
Verlag
Springer Netherlands
Erschienen in
Clinical & Experimental Metastasis / Ausgabe 8/2014
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-014-9674-1

Weitere Artikel der Ausgabe 8/2014

Clinical & Experimental Metastasis 8/2014 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.