Investigational serine/threonine kinase inhibitors against prostate cancer metastases

References

• Wadosky KM, Koochekpour S. Molecular mechanisms underlying resistance to androgen deprivation therapy in prostate cancer. Oncotarget. 2016;7:64447-644470.
   Web of Science ®Google Scholar
• Shiota M, Yokomizo A, Naito S. Increased androgen receptor transcription: a cause of castration-resistant prostate cancer and a possible therapeutic target. J Mol Endocrinol. 2011;47:25–41.
   Web of Science ®Google Scholar
• Alex AB, Pal SK, Agarwal N. CYP17 inhibitors in prostate cancer: latest evidence and clinical potential. Ther Adv Med Oncol. 2016;8:267–275.
   PubMed Web of Science ®Google Scholar
• Caffo O, Maines F, Veccia A, et al. Splice variants of androgen receptor and prostate cancer. Oncol Rev. 2016;10:297.
   PubMed Web of Science ®Google Scholar
• Perner S, Cronauer MV, Schrader AJ, et al. Adaptive responses of androgen receptor signaling in castration-resistant prostate cancer. Oncotarget. 2015;6:35542–35555.
   PubMed Web of Science ®Google Scholar
• Gravina GL, Festuccia C, Galatioto GP, et al. Surgical and biologic outcomes after neoadjuvant bicalutamide treatment in prostate cancer. Urology. 2007;70:728–733.
   PubMed Web of Science ®Google Scholar
• Traish AM. Morgentaler a epidermal growth factor receptor expression escapes androgen regulation in prostate cancer: a potential molecular switch for tumour growth. Br J Cancer. 2009;101:1949–1956.
   PubMed Web of Science ®Google Scholar
• Festuccia C, Gravina GL, Muzi P, et al. Bicalutamide increases phospho-Akt levels through Her2 in patients with prostate cancer. Endocr Relat Cancer. 2007;14:601–611.
   PubMed Web of Science ®Google Scholar
• Wu JD, Haugk K, Woodke L, et al. Interaction of IGF signaling and the androgen receptor in prostate cancer progression. J Cell Biochem. 2006;99:392–401.
   PubMed Web of Science ®Google Scholar
• Terry S, Beltran H. The many faces of neuroendocrine differentiation in prostate cancer progression. Front Oncol. 2014;4:60.
   PubMedGoogle Scholar
• Liu C, Zhu Y, Lou W, et al. Inhibition of constitutively active Stat3 reverses enzalutamide resistance in LNCaP derivative prostate cancer cells. Prostate. 2014;74:201–209.
   PubMed Web of Science ®Google Scholar
• Silberstein JL, Taylor MN, Antonarakis ES. Novel insights into molecular indicators of response and resistance to modern androgen-axis therapies in prostate cancer. Curr Urol Rep. 2016;17:29.
   PubMed Web of Science ®Google Scholar
• Revelos K, Petraki C, Gregorakis A, et al. Immunohistochemical expression of Bcl2 is an independent predictor of time-to-biochemical failure in patients with clinically localized prostate cancer following radical prostatectomy. Anticancer Res. 2005;25:3123–3133.
   PubMed Web of Science ®Google Scholar
• Capra M, Nuciforo PG, Confalonieri S, et al. Frequent alterations in the expression of serine/threonine kinases in human cancers. Cancer Res. 2006;66:8147–8154.
   PubMed Web of Science ®Google Scholar
• El-Amm J, Aragon-Ching JB. Targeting bone metastases in metastatic castration-resistant prostate cancer. Clin Med Insights Oncol. 2016;10:11–19.
   PubMed Web of Science ®Google Scholar
• Babcook MA, Shukla S, Fu P, et al. Synergistic simvastatin and metformin combination chemotherapy for osseous metastatic castration-resistant prostate cancer. Mol Cancer Ther. 2014;13:2288–2302.
   PubMed Web of Science ®Google Scholar
• Irelli A, Bruera G, Cannita K, et al. Bioclinical parameters driving decision-making of subsequent lines of treatment in metastatic castration-resistant prostate cancer. Biomed Res Int. 2014;909623. Available from: http://dx.doi.org/10.1155/2014/909623
   PubMed Web of Science ®Google Scholar
• Roviello G, Sigala S, Sandhu S, et al. Role of the novel generation of androgen receptor pathway targeted agents in the management of castration-resistant prostate cancer: A literature based meta-analysis of randomized trials. Eur J Cancer. 2016;61:111–121.
   PubMed Web of Science ®Google Scholar
• Gravina GL, Senapedis W, McCauley D, et al. Nucleo-cytoplasmic transport as a therapeutic target of cancer. J Hematol Oncol. 2014;7:85.
   PubMed Web of Science ®Google Scholar
• Hinck AP, O’Connor-McCourt MD. Structures of TGF-β receptor complexes: implications for function and therapeutic intervention using ligand traps. Curr Pharm Biotechnol. 2011;12:2081–2098.
   PubMed Web of Science ®Google Scholar
• Cornford P, Bellmunt J, Bolla M, et al. 2016. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer. Eur Urol Aug 31. doi: 10.1016/j.eururo.2016.08.002. [Epub ahead of print].
   Google Scholar
• Huo R, Wang L, Liu P, et al. Cabazitaxel-induced autophagy via the PI3K/Akt/mTOR pathway contributes to A549 cell death. Mol Med Rep. 2016;14:3013–3020.
   PubMed Web of Science ®Google Scholar
• Boudadi K, Antonarakis ES. Resistance to novel antiandrogen therapies in metastatic castration-resistant prostate cancer. Clin Med Insights Oncol. 2016;10:1–9.
   PubMed Web of Science ®Google Scholar
• Shiota M, Bishop JL, Takeuchi A, et al. Inhibition of the HER2-YB1-AR axis with Lapatinib synergistically enhances Enzalutamide anti-tumor efficacy in castration resistant prostate cancer. Oncotarget. 2015;6:9086–9098.
   PubMed Web of Science ®Google Scholar
• Dang Q, Li L, Xie H, et al. Anti-androgen enzalutamide enhances prostate cancer neuroendocrine (NE) differentiation via altering the infiltrated mast cells → androgen receptor (AR) → miRNA32 signals. Mol Oncol. 2015;9:1241–1251.
   PubMed Web of Science ®Google Scholar
• Friedlander TW, Weinberg VK, Small EJ, et al. Effect of the somatostatin analog octreotide acetate on circulating insulin-like growth factor-1 and related peptides in patients with non-metastatic castration-resistant prostate cancer: results of a phase II study. Urol Oncol. 2012;30:408–414.
   PubMed Web of Science ®Google Scholar
• Vale CL, Burdett S, Rydzewska LH, et al. STOpCaP steering group. Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data. Lancet Oncol. 2016;17:243–256.
   PubMed Web of Science ®Google Scholar
• Lipton A, Fizazi K, Stopeck AT, et al. Effect of denosumab versus zoledronic acid in preventing skeletal-related events in patients with bone metastases by baseline characteristics. Eur J Cancer. 2016;53:75–83.
   PubMed Web of Science ®Google Scholar
• Barcellos-de-Souza P, Comito G, Pons-Segura C, et al. Mesenchymal stem cells are recruited and activated into carcinoma-associated fibroblasts by prostate cancer microenvironment-derived TGF-β1. Stem Cells. 2016 Jun 14;34:2536–2547.
   PubMed Web of Science ®Google Scholar
• Wallerand H, Robert G, Pasticier G, et al. The epithelial-mesenchymal transition-inducing factor TWIST is an attractive target in advanced and/or metastatic bladder and prostate cancers. Urol Oncol. 2010;28:473–479.
   PubMed Web of Science ®Google Scholar
• Li P, Yang R, Gao WQ. Contributions of epithelial-mesenchymal transition and cancer stem cells to the development of castration resistance of prostate cancer. Mol Cancer. 2014;13:55.
   PubMed Web of Science ®Google Scholar
• Yokoyama NN, Shao S, Hoang BH, et al. Wnt signaling in castration-resistant prostate cancer: implications for therapy. Am J Clin Exp Urol. 2014;2:27–44.
   PubMedGoogle Scholar
• Lu Q, Liu Z, Li Z, et al. TIPE2 Overexpression Suppresses the Proliferation, Migration, and Invasion in Prostate Cancer Cells by Inhibiting PI3K/Akt Signaling Pathway. Oncol Res. 2016;24:305–313.
   Google Scholar
• Statz CM, Patterson SE, Mockus SM. mTOR inhibitors in castration-resistant prostate cancer: a systematic review. Target Oncol. 2016 Aug 9. doi:10.1007/s11523-016-0453-6
   PubMed Web of Science ®Google Scholar
• Edlind MP, Hsieh AC. PI3K-AKT-mTOR signaling in prostate cancer progression and androgen deprivation therapy resistance. Asian J Androl. 2014;16:378–386.
   PubMed Web of Science ®Google Scholar
• Gravina GL, Mancini A, Rucci N, et al. Effects of dual PI3K/mTOR inhibition on incidence and local growth of prostate cancer bone metastases. Anticancer Research. 2012;32:1854–1855.
   Web of Science ®Google Scholar
• Papatsoris AG, Karamouzis MV, Athanasios G. Papavassiliou. The power and promise of “rewiring” the mitogen-activated protein kinase network in prostate cancer therapeutics. Mol Cancer Ther. 2007;6:811–819.
   PubMed Web of Science ®Google Scholar
• Browne AJ, Göbel A, Thiele S, et al. p38 MAPK regulates the Wnt inhibitor Dickkopf-1 in osteotropic prostate cancer cells. Cell Death Dis. 2016;7:e2119.
   PubMed Web of Science ®Google Scholar
• Fritz RD, Pertz O. The dynamics of spatio-temporal Rho GTPase signaling: formation of signaling patterns. F1000Res. 2016;5:749.
   PubMedGoogle Scholar
• Chin VT, Nagrial AM, Chou A, et al. Rho-associated kinase signalling and the cancer microenvironment: novel biological implications and therapeutic opportunities. Expert Rev Mol Med. 2015;17:e17.
   PubMed Web of Science ®Google Scholar
• Senapedis W1, Crochiere M, Baloglu E, et al. Therapeutic potential of targeting PAK signaling. Anticancer Agents Med Chem. 2016;16:75–88.
   PubMed Web of Science ®Google Scholar
• Kumar R, Li DQ. PAKs in human cancer progression: from inception to cancer therapeutic to future oncobiology. Adv Cancer Res. 2016;130:137–209.
   PubMed Web of Science ®Google Scholar
• Kichina JV1, Goc A, Al-Husein B, et al. PAK1 as a therapeutic target. Expert Opin Ther Targets. 2010;14:703–725.
   PubMed Web of Science ®Google Scholar
• Whale AD, Dart A, Holt M, et al. PAK4 kinase activity and somatic mutation promote carcinoma cell motility and influence inhibitor sensitivity. Oncogene. 2013;32:2114–2120.
   PubMed Web of Science ®Google Scholar
• Morse EM, Sun X, Olberding JR, et al. PAK6 targets to cell-cell adhesions through its N-terminus in a Cdc42-dependent manner to drive epithelial colony escape. J Cell Sci. 2016;129:380–393.
   PubMed Web of Science ®Google Scholar
• Pasche B, Pennison MJ, Jimenez H, et al. TGFBR1 and cancer susceptibility. Trans Am Clin Climatol Assoc. 2014;125:300–312.
   PubMedGoogle Scholar
• Gravina GL, Mancini A, Rucci N, et al. Effects of 1D11 an antibody against transforming growth factor beta (TGF-B) on incidence and local growth of prostate cancer bone metastases. Eur J Cancer. 2012;48(S5):S236.
   Google Scholar
• Zhang Q, Chen L, Helfand BT, et al. TGF-β regulates DNA methyltransferase expression in prostate cancer, correlates with aggressive capabilities, and predicts disease recurrence. Plos One. 2011;6:e25168.
   PubMed Web of Science ®Google Scholar
• Jaschinski F, Rothhammer T, Jachimczak P, et al. The antisense oligonucleotide trabedersen (AP 12009) for the targeted inhibition of TGF-β2. Curr Pharm Biotechnol. 2011;12:2203–2213.
   PubMed Web of Science ®Google Scholar
• Harrison CA, Gray PC, Vale WW, et al. Antagonists of activin signaling: mechanisms and potential biological applications. Trends Endocrinol Metab. 2005;16:73–78.
   PubMed Web of Science ®Google Scholar
• Herbertz S, Sawyer JS, Stauber AJ, et al. Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway. Drug Des Devel Ther. 2015;9:4479–4499.
   PubMed Web of Science ®Google Scholar
• Fabregat I, Fernando J, Mainez J, et al. TGF-beta signaling in cancer treatment. Curr Pharm Des. 2014;20:2934–2947.
   PubMed Web of Science ®Google Scholar
• Gao Y, Ishiyama H, Sun M, et al. The alkylphospholipid, perifosine, radiosensitizes prostate cancer cells both in vitro and in vivo. Radiat Oncol. 2011;6:39.
   PubMed Web of Science ®Google Scholar
• Festuccia C, Gravina GL, Muzi P, et al. Akt down-modulation induces apoptosis of human prostate cancer cells and synergizes with EGFR tyrosine kinase inhibitors. Prostate. 2008;68:965–974.
   PubMed Web of Science ®Google Scholar
• Chee KG, Longmate J, Quinn DI, et al. The AKT inhibitor perifosine in biochemically recurrent prostate cancer: a phase II California/Pittsburgh cancer consortium trial. Clin Genitourin Cancer. 2007;5:433–437.
   PubMed Web of Science ®Google Scholar
• Lamoureux F, Thomas C, Crafter C, et al. Blocked autophagy using lysosomotropic agents sensitizes resistant prostate tumor cells to the novel Akt inhibitor AZD5363. Clin Cancer Res. 2013;19:833–844.
   PubMed Web of Science ®Google Scholar
• Thomas C1, Lamoureux F, Crafter C, et al. Synergistic targeting of PI3K/AKT pathway and androgen receptor axis significantly delays castration-resistant prostate cancer progression in vivo. Mol Cancer Ther. 2013;12:2342–2355.
   PubMed Web of Science ®Google Scholar
• Blake JF, Xu R, Bencsik JR, et al. Discovery and preclinical pharmacology of a selective ATP-competitive Akt inhibitor (GDC-0068) for the treatment of human tumors. J Med Chem. 2012;55:8110–8127.
   PubMed Web of Science ®Google Scholar
• Templeton AJ1, Dutoit V, Cathomas R, et al. Swiss group for clinical cancer research (SAKK). Phase 2 trial of single-agent everolimus in chemotherapy-naive patients with castration-resistant prostate cancer (SAKK 08/08). Eur Urol. 2013;64:150–158.
   PubMed Web of Science ®Google Scholar
• Armstrong AJ, Netto GJ, Rudek MA, et al. A pharmacodynamic study of rapamycin in men with intermediate- to high-risk localized prostate cancer. Clin Cancer Res. 2010;16:3057–3066.
   PubMed Web of Science ®Google Scholar
• Courtney KD, Manola JB, Elfiky AA, et al. A phase I study of everolimus and docetaxel in patients with castration-resistant prostate cancer. Clin Genitourin Cancer. 2015;13:113–123.
   PubMed Web of Science ®Google Scholar
• Rathkopf DE, Larson SM, Anand A, et al. Everolimus combined with gefitinib in patients with metastatic castration-resistant prostate cancer: Phase 1/2 results and signaling pathway implications. Cancer. 2015;121:3853–3861.
   PubMed Web of Science ®Google Scholar
• Nakabayashi M, Werner L, Courtney KD, et al. Phase II trial of RAD001 and bicalutamide for castration-resistant prostate cancer. BJU Int. 2012;110:1729–1735.
   PubMed Web of Science ®Google Scholar
• Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2010;32:247–288.
   PubMedGoogle Scholar
• Bayés M1, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2005;27:331–372.
   PubMedGoogle Scholar
• Armstrong AJ, Shen T, Halabi S, et al. A phase II trial of temsirolimus in men with castration-resistant metastatic prostate cancer. Clin Genitourin Cancer. 2013;11:397–406.
   PubMed Web of Science ®Google Scholar
• Kruczek K, Ratterman M, Tolzien K, et al. A phase II study evaluating the toxicity and efficacy of single-agent temsirolimus in chemotherapy-naïve castration-resistant prostate cancer. Br J Cancer. 2013;109:1711–1716.
   PubMed Web of Science ®Google Scholar
• Emmenegger U, Booth CM, Berry S, et al. Temsirolimus maintenance therapy after docetaxel induction in castration-resistant prostate cancer. Oncologist. 2015;20:1351–1352.
   PubMed Web of Science ®Google Scholar
• Weinberg MA. RES-529: a PI3K/AKT/mTOR pathway inhibitor that dissociates the mTORC1 and mTORC2 complexes. Anticancer Drugs. 2016;27:475–487.
   Web of Science ®Google Scholar
• Gravina GL, Marampon F, Sherris D, et al. Torc1/Torc2 inhibitor, Palomid 529, enhances radiation response modulating CRM1-mediated survivin function and delaying DNA repair in prostate cancer models. Prostate. 2014;74:852–868.
   PubMed Web of Science ®Google Scholar
• Gravina GL, Marampon F, Petini F, et al. The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormonerefractory prostate cancer cells. Endocr Relat Cancer. 2011;18:385–400.
   PubMed Web of Science ®Google Scholar
• Jiang SJ, Wang S. Dual targeting of mTORC1 and mTORC2 by INK-128 potently inhibits human prostate cancer cell growth in vitro and in vivo. Tumour Biol. 2015;36:8177–8184.
   PubMed Web of Science ®Google Scholar
• Gravina GL, Mancini A, Scarsella L, et al. Dual PI3K/mTOR inhibitor, XL765 (SAR245409), shows superior effects to sole PI3K [XL147 (SAR245408)] or mTOR [rapamycin] inhibition in prostate cancer cell models. Tumour Biol. 2016;37:341–351.
   PubMed Web of Science ®Google Scholar
• Maik-Rachline G, Seger R. The ERK cascade inhibitors: towards overcoming resistance. Drug Resist Updat. 2016;25:1–12.
   PubMed Web of Science ®Google Scholar
• Shi Y, Wu J, Mick R, et al. Farnesyltransferase inhibitor effects on prostate tumor micro-environment and radiation survival. Prostate. 2005;62:69–82.
   PubMed Web of Science ®Google Scholar
• Sebti S, Hamilton AD. Inhibitors of prenyl transferases. Curr Opin Oncol. 1997;9:557–561.
   PubMedGoogle Scholar
• Desrosiers RR, Cusson MH, Turcotte S, et al. Farnesyltransferase inhibitor SCH-66336 downregulates secretion of matrix proteinases and inhibits carcinoma cell migration. Int J Cancer. 2005;114:702–712.
   PubMed Web of Science ®Google Scholar
• Wlodarczyk N, Le Broc-Ryckewaert D, Gilleron P, et al. Potent farnesyltransferase inhibitors with 1,4-diazepane scaffolds as novel destabilizing microtubule agents in hormone-resistant prostate cancer. J Med Chem. 2011;54:1178–1190.
   PubMed Web of Science ®Google Scholar
• Fu Z, Smith PC, Zhang L, et al. Effects of raf kinase inhibitor protein expression on suppression of prostate cancer metastasis. J Natl Cancer Inst. 2003;95:878–889.
   PubMed Web of Science ®Google Scholar
• Yousuf S, Duan M, Moen EL, et al. Raf kinase inhibitor protein (RKIP) blocks signal transducer and activator of transcription 3 (STAT3) activation in breast and prostate cancer. Plos One. 2014;9:e92478.
   PubMed Web of Science ®Google Scholar
• Rachner TD, Göbel A, Browne A, et al. P38 regulates the Wnt inhibitor dickkopf-1 in breast cancer. Biochem Biophys Res Commun. 2015;466:728–732.
   PubMed Web of Science ®Google Scholar
• Caverzasio J, Manen D. Essential role of Wnt3a-mediated activation of mitogen-activated protein kinase p38 for the stimulation of alkaline phosphatase activity and matrix mineralization in C3H10T1/2 mesenchymal cells. Endocrinology. 2007;148:5323–5330.
   PubMed Web of Science ®Google Scholar
• Kamiya N, Kobayashi T, Mochida Y, et al. Wnt inhibitors Dkk1 and Sost are downstream targets of BMP signaling through the type IA receptor (BMPRIA) in osteoblasts. J Bone Miner Res. 2010;25:200–210.
   PubMed Web of Science ®Google Scholar
• Yumoto K, Eber MR, Berry JE, et al. Molecular pathways: niches in metastatic dormancy. Clin Cancer Res. 2014;20:3384–3389.
   PubMed Web of Science ®Google Scholar
• Sosa MS, Avivar-Valderas A, Bragado P, et al. ERK1/2 and p38α/β signaling in tumor cell quiescence: opportunities to control dormant residual disease. Clin Cancer Res. 2011;17:5850–5857.
   PubMed Web of Science ®Google Scholar
• Vue B, Zhang S, Chen QH. Flavonoids with therapeutic potential in prostate cancer. Anticancer Agents Med Chem. 2016;16:1205–1229.
   PubMed Web of Science ®Google Scholar
• Gioti K, Tenta R. Bioactive natural products against prostate cancer: mechanism of action and autophagic/apoptotic molecular pathways. Planta Med. 2015;81:543–562.
   PubMed Web of Science ®Google Scholar
• Jiang WG, Sanders AJ, Katoh M, et al. Tissue invasion and metastasis: molecular, biological and clinical perspectives. Semin Cancer Biol. 2015;35:S244–75.
   PubMed Web of Science ®Google Scholar
• Shah S, Savjani J. A review on ROCK-II inhibitors: from molecular modelling to synthesis. Bioorg Med Chem Lett. 2016;26:2383–2391.
   PubMed Web of Science ®Google Scholar
• Pranatharthi A, Ross C, Srivastava S. Cancer stem cells and radioresistance: Rho/ROCK pathway plea attention. Stem Cells Int. 2016;2016:5785786.
   PubMed Web of Science ®Google Scholar
• Matsubara M, Bissell MJ. Inhibitors of Rho kinase (ROCK) signaling revert the malignant phenotype of breast cancer cells in 3D context. Oncotarget. 2016;7:31602–31622.
   PubMed Web of Science ®Google Scholar
• Manetti F. LIM kinases are attractive targets with many macromolecular partners and only a few small molecule regulators. Med Res Rev. 2012;32:968–998.
   PubMed Web of Science ®Google Scholar
• Aslan JE, Baker SM, Loren CP, et al. The PAK system links Rho GTPase signaling to thrombin-mediated platelet activation. Am J Physiol Cell Physiol. 2013;305:C519–28.
   PubMed Web of Science ®Google Scholar
• Bhardwaj A, Srivastava SK, Singh S, et al. CXCL12/CXCR4 signaling counteracts docetaxel-induced microtubule stabilization via p21-activated kinase 4-dependent activation of LIM domain kinase 1. Oncotarget. 2014;5:11490–11500.
   PubMed Web of Science ®Google Scholar
• Mardilovich K, Gabrielsen M, McGarry L, et al. Elevated LIM kinase 1 in nonmetastatic prostate cancer reflects its role in facilitating androgen receptor nuclear translocation. Mol Cancer Ther. 2015;14:246–258.
   PubMed Web of Science ®Google Scholar
• Gajos-Michniewicz A, Czyz M. Modulation of WNT/β-catenin pathway in melanoma by biologically active components derived from plants. Fitoterapia. 2016;109:283–292.
   PubMed Web of Science ®Google Scholar
• Cho HJ, Lim Do Y, Kwon GT, et al. Benzyl isothiocyanate inhibits prostate cancer development in the transgenic adenocarcinoma mouse prostate (TRAMP) model, which is associated with the induction of cell cycle G1 arrest. Int J Mol Sci. 2016;17:264.
   PubMed Web of Science ®Google Scholar
• Zhu KC, Sun JM, Shen JG, et al. Afzelin exhibits anti-cancer activity against androgen-sensitive LNCaP and androgen-independent PC-3 prostate cancer cells through the inhibition of LIM domain kinase 1. Oncol Lett. 2015;10:2359–2365.
   PubMed Web of Science ®Google Scholar
• Catto JW, Alcaraz A, Bjartell AS, et al. MicroRNA in prostate, bladder, and kidney cancer: a systematic review. Eur Urol. 2011;59:671–681.
   PubMed Web of Science ®Google Scholar
• Cai S, Chen R, Li X, et al. Downregulation of microRNA-23a suppresses prostate cancer metastasis by targeting the PAK6-LIMK1 signaling pathway. Oncotarget. 2015;6:3904–3917.
   PubMed Web of Science ®Google Scholar
• Hailer A, Grunewald TG, Orth M, et al. Loss of tumor suppressor mir-203 mediates overexpression of LIM and SH3 Protein 1 (LASP1) in high-risk prostate cancer thereby increasing cell proliferation and migration. Oncotarget. 2014;5:2918–4153.
   PubMed Web of Science ®Google Scholar
• Saini S, Majid S, Yamamura S, et al. Regulatory Role of mir-203 in Prostate Cancer Progression and Metastasis. Clin Cancer Res. 2011;17:5287–5298.
   PubMed Web of Science ®Google Scholar
• Majid S, Dar AA, Saini S, et al. miRNA-34b inhibits prostate cancer through demethylation, active chromatin modifications, and AKT pathways. Clin Cancer Res. 2013;19:73–84.
   PubMed Web of Science ®Google Scholar
• Qiu X, Zhu J, Sun Y, et al. TR4 nuclear receptor increases prostate cancer invasion via decreasing the miR-373-3p expression to alter TGFβR2/p-Smad3 signals. Oncotarget. 2015;6:15397–15409.
   PubMed Web of Science ®Google Scholar
• Cai S, Li X, Chen R, et al. Impact of miRNA-23a-p21-activated kinase 6 signaling on the migration and invasion activities of prostate cancer cells. Chin J Exp Surg. 2012;29:1360–1362.
   Google Scholar
• Sheth S, Jajoo S, Kaur T, et al. Resveratrol reduces prostate cancer growth and metastasis by inhibiting the Akt/MicroRNA-21 pathway. Plos One. 2012;7:e51655.
   PubMed Web of Science ®Google Scholar
• Lin ZY, Huang YQ, Zhang YQ, et al. MicroRNA-224 inhibits progression of human prostate cancer by downregulating TRIB1. Int J Cancer. 2014;135:541–550.
   PubMed Web of Science ®Google Scholar
• Dangi-Garimella S, Yun J, Eves EM, et al. Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7. Embo J. 2009;28:347–358.
   PubMed Web of Science ®Google Scholar
• Boegemann M, Schrader AJ, Krabbe LM, et al. Present, emerging and possible future biomarkers in castration resistant prostate cancer (CRPC). Curr Cancer Drug Targets. 2015;15:243–255.
   PubMed Web of Science ®Google Scholar
• Wen X, Deng FM, Wang J. MicroRNAs as predictive biomarkers and therapeutic targets in prostate cancer. Am J Clin Exp Urol. 2014;2:219–230.
   PubMedGoogle Scholar
• Bienz M, Saad F. Androgen-deprivation therapy and bone loss in prostate cancer patients: a clinical review. Bonekey Rep. 2015;4:716.
   PubMed Web of Science ®Google Scholar
• Cheung AS, Zajac JD, Grossmann M. Muscle and bone effects of androgen deprivation therapy: current and emerging therapies. Endocr Relat Cancer. 2014;21:R371–94.
   PubMed Web of Science ®Google Scholar
• Iranikhah M, Stricker S, Freeman MK. Future of bisphosphonates and denosumab for men with advanced prostate cancer. Cancer Manag Res. 2014;6:217–224.
   PubMed Web of Science ®Google Scholar
• Chagin AS. Effectors of mTOR-autophagy pathway: targeting cancer, affecting the skeleton. Curr Opin Pharmacol. 2016;28:1–7.
   PubMed Web of Science ®Google Scholar
• Liu DM, Zhao L, Liu TT, et al. Rictor/mTORC2 loss in osteoblasts impairs bone mass and strength. Bone. 2016;90:50–58.
   PubMed Web of Science ®Google Scholar
• Smink JJ, Leutz A. Rapamycin and the transcription factor C/EBPbeta as a switch in osteoclast differentiation: implications for lytic bone diseases. J Mol Med (Berl). 2010;88:227–233.
   PubMed Web of Science ®Google Scholar