Neuroendocrine differentiation in prostate cancer: Current and emerging therapy strategies

Critical Reviews in Oncology/Hematology

Volumn 92, Issue 1, 2014, Pages 11-24

  Conteduca, Vincenza ^a   Aieta, Michele ^b   Amadori, Dino ^a   De Giorgi, Ugo ^a  

^a DEPARTMENT OF MEDICAL ONCOLOGY   (Italy)

^b REFERRAL CANCER CENTER OF BASILICATA   (Italy)

Author keywords

Androgen deprivation therapy; Cancer stem cells; Chromogranin A; Epithelial mesenchymal transition; Neuroendocrine differentiation; Prognosis; Prostate cancer; Somatostatin

Indexed keywords

ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; AURORA KINASE INHIBITOR; BOMBESIN ANTAGONIST; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MICRORNA; SARACATINIB; SEROTONIN ANTAGONIST; SHORT HAIRPIN RNA; SOMATOSTATIN DERIVATIVE; ZOLEDRONIC ACID;

CANCER CHEMOTHERAPY; CANCER PROGNOSIS; CANCER STEM CELL; DIAGNOSTIC IMAGING; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; MOLECULAR PATHOLOGY; NEUROENDOCRINE DIFFERENTIATION; NONHUMAN; ONCOLOGICAL PARAMETERS; PROSTATE CANCER; REVIEW; SIGNAL TRANSDUCTION; TUMOR MICROENVIRONMENT; TUMOR VASCULARIZATION; CELL DIFFERENTIATION; DISEASE COURSE; DRUG EFFECTS; GENETICS; MALE; METABOLISM; NEUROENDOCRINE TUMORS; PATHOLOGY; PROGNOSIS; PROSTATIC NEOPLASMS;

CELL DIFFERENTIATION; DISEASE PROGRESSION; EPITHELIAL-MESENCHYMAL TRANSITION; HUMANS; MALE; NEOPLASTIC STEM CELLS; NEUROENDOCRINE TUMORS; PROGNOSIS; PROSTATIC NEOPLASMS;

EID: 84906937466     PISSN: 10408428     EISSN: 18790461     Source Type: Journal    
DOI: 10.1016/j.critrevonc.2014.05.008     Document Type: Review

References (108)

1. Di Sant'Agnese P.A. Neuroendocrine differentiation in prostatic carcinoma: an update on recent developments. Ann Oncol 2001, 12(Suppl. 2):135-140.
2. Volante M., Rindi G., Papotti M. The grey zone between pure (neuro)endocrine and non-(neuro)endocrine tumors: a comment on concepts and classification of mixed exocrine-endocrine neoplasms. Virchows Arch 2006, 449(5):499-506.
3. Huang J., Yao J.L., di Sant'Agnese P.A., Yang Q., Bourne P.A., Na Y. Immunohistochemical characterization of neuroendocrine cells in prostate cancer. Prostate 2006, 66:1399-1406.
4. Grobholz R., Griebe M., Sauer C.G., Michel M.S., Trojan L., Bleyl U. Influence neuroendocrine tumor cells on proliferation in prostatic carcinoma. Hum Pathol 2005, 36:562-570.
5. Segal L., Cohen F., Huffejee Z., Savage N. Bcl2 protooncogene expression in prostate cancer and its relationship to the prostatic neuroendocrine cell. Arch Pathol Lab Med 1994, 118:616-618.
6. Chen H., Sun Y., Wu C., et al. Pathogenesis of prostatic small cell carcinoma involves the inactivation of the P53 pathway. Endocr Relat Cancer 2012, 19:321-331.
7. Sun Y., Niu J., Huang J. Neuroendocrine differentiation in prostate cancer. Am J Transl Res 2009, 1:148-162.
8. Palapattu G.S., Wu C., Silvers C.R., et al. Selective expression of CD44, a putative prostate cancer stem cell marker, in neuroendocrine tumor cells of human prostate cancer. Prostate 2009, 69:787-798.
9. Richardson G.D., Robson C.N., Lang S.H., Neal D.E., Maitland N.J., Collins A.T. CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci 2004, 117:3539-3545.
10. Yuan T.C., Veeramani S., Ming-Fong Lin M.F. Neuroendocrine-like prostate cancer cells: neuroendocrine transdifferentiation of prostate adenocarcinoma cells. Endocr Relat Cancer 2007, 14:531-547.
11. Dizeyi N., Bjartell A., Nilsson E., et al. Expression of serotonin receptors and role of serotonin in human prostate cancer tissue and cell lines. Prostate 2004, 59:328-336.
12. Iwamura M., Wu G., Abrahamsson P.A., di Sant'Agnese P.A., Cockett A.T., Deftos L.J. Parathyroid hormone-related protein is expressed by prostatic neuroendocrine cells. Urology 1994, 43:667-674.
13. Nelson E.C., Cambio A.J., Yang J.C., Ok J.H., Lara P.N., Evans C.P. Clinical implications of neuroendocrine differentiation in prostate cancer. Prostate Cancer Prostatic Dis 2007, 10:6-14.
14. Beltran H., Rickman D.S., Park K., et al. Molecular Characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov 2011, 1:487-495.
15. Mosquera J.M., Beltran H., Park K., et al. Concurrent AURKA and MYCN gene amplifications are harbingers of lethal treatment-related neuroendocrine prostate cancer. Neoplasia 2013, 15:1-10.
16. Borre M., Nerstrom B., Overgaard J. Association between immunohistochemical expression of vascular endothelial growth factor (VEGF), VEGF-expressing neuroendocrine differentiated tumor cells, and outcome in prostate cancer patients subjected to watchful waiting. Clin Cancer Res 2000, 6:1882-1890.
17. Heinrich E., Trojan L., Friedrich D., et al. Neuroendocrine tumor cells in prostate cancer: evaluation of the neurosecretory products serotonin, bombesin, and gastrin-impact on angiogenesis and clinical follow-up. Prostate 2011, 71:1752-1758.
18. Qi J., Nakayama K., Cardiff R.D., et al. Siah2-dependent concerted activity of HIF & FoxA2 regulates formation of neuroendocrine phenotype & neuroendocrine prostate tumors. Cancer Cell 2010, 18:23-38.
19. Humez S., Monet M., Legrand G., Lepage G., Delcourt P., Prevarskaya N. Epidermal growth factor-induced neuroendocrine differentiation and apoptotic resistance of androgen-independent human prostate cancer cells. Endocr Relat Cancer 2006, 13:181-195.
20. Rapa I., Volante M., Migliore C., et al. Human ASH-1 promotes neuroendocrine differentiation in androgen deprivation conditions and interferes with androgen responsiveness in prostate cancer cells. Prostate 2013, 73(11):1241-1249.
21. Rapa I., Ceppi P., Bollito E., et al. Human ASH1 expression in prostate cancer with neuroendocrine differentiation. Mod Pathol 2008, 21:700-707.
22. Jongsma J., Oomen M.H., Noordzij M.A., et al. Androgen deprivation of the PC-310 [correction of prohormone convertase-310] human prostate cancer model system induces neuroendocrine differentiation. Cancer Res 2000, 60:741-748.
23. Jongsma J., Oomen M.H., Noordzij M.A., et al. Different profiles of neuroendocrine cell differentiation evolve in the PC-310 human prostate cancer model during long-term androgen deprivation. Prostate 2000, 50:203-215.
24. Ahigren G., Pedersen K., Lundberg S., Aus G., Hugosson J., Abrahamsson P.A. Regressive changes and neuroendocrine differentiation in prostate cancer after neoadjuvant hormonal treatment. Prostate 2000, 42:274-279.
25. Jiborn T., Bjartell A., Abrahamsson P.A. Neuroendocrine differentiation in prostatic carcinoma during hormonal treatment. Urology 1998, 51:585-589.
26. Spiotto M.T., Chung T.D. STAT3 mediates IL-6-induced neuroendocrine differentiation in prostate cancer cells. Prostate 2000, 42:186-195.
27. Lee L.F., Louie M.C., Desai S.J., et al. Interleukin-8 confers androgen-independent growth and migration of LNCaP: differential effects of tyrosine kinases Src and FAK. Oncogene 2004, 23:2197-2205.
28. Liu Q., Russell M.R., Shahriari K., et al. Interleukin-1β promotes skeletal colonization and progression of metastatic prostate cancer cells with neuroendocrine features. Cancer Res 2013, 73:3297-3305.
29. Wu C., Huang J. Phosphatidylinositol 3-Kinase-AKT-mammalian target of rapamycin pathway is essential for neuroendocrine differentiation of prostate cancer. J Biol Chem 2006, 282:3571-3583.
30. Uysal-Onganer P., Kawano Y., Caro M., et al. Wnt-11 promotes neuroendocrine-like differentiation, survival and migration of prostate cancer cells. Mol Cancer 2010, 9:55.
31. Pernicová Z., Slabáková E., Kharaishvili G., et al. Androgen depletion induces senescence in prostate cancer cells through down-regulation of Skp2. Neoplasia 2011, 13(6):526-536.
32. Bonkhoff H. Neuroendocrine differentiation in human prostate cancer. Morphogenesis, proliferation and androgen receptor status. Ann Oncol 2001, 12(Suppl. 2):141-144.
33. Bonkhoff H., Wernert N., Dhom G., et al. Relation of endocrine-paracrine cells to cell proliferation in normal, hyperplastic and neoplastic human prostate. Prostate 1991, 19:91-98.
34. Yuan T.C., Veeramani S., Lin F.F., et al. Androgen deprivation induces human prostate epithelial neuroendocrine differentiation of androgen-sensitive LNCaP cells. Endocr Relat Cancer 2006, 13:151-157.
35. McDonnell T.J., Troncoso P., Brisbay S.M., et al. Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res 1992, 52:6940-6944.
36. Fixemer T., Remberger K., Bonkhoff H. Apoptosis resistance of neuroendocrine phenotypes in prostatic adenocarcinoma. Prostate 2002, 53:118-123.
37. Xing N., Qian J., Botswick D., Bergstralh E., Young C.Y. Neuroendocrine cells in human prostate over-express the anti-apoptosis protein survivin. Prostate 2001, 48:7-15.
38. Huang J., Yao J.L., Zhang L., et al. Differential expression of interleukin-8 and its receptors in the neuroendocrine and non neuroendocrine compartments of prostatencancer. Am J Pathol 2005, 166:1807-1815.
39. Choi S.Y., Gout P.W., Collins C.C., Wang Y. Epithelial immune cell-like transition (EIT): a proposed transdifferentiation process underlying immune-suppressive activity of epithelial cancers. Differentiation 2012, 83:293-298.
40. Jordan C.T., Guzman M.L., Noble M. Cancer stem cells. N Engl J Med 2006, 355:1253-1261.
41. Tu S.M., Lin S.H. Prostate cancer stem cells. Clin Genitourin Cancer 2012, 10:69-76.
42. Foster B.A., Gangavarapu K.J., Mathew G., et al. Human prostate side population cells demonstrate stem cell properties in recombination with urogenital sinus mesenchyme. PLOS ONE 2013, 8(1):e55062.
43. Vander Griend D.J., Karthaus W.L., Dalrymple S., et al. The role of CD133 in normal human prostate stem cells and malignant cancer-initiating cells. Cancer Res 2008, 68:9703-9711.
44. Wang X., Kruithof-de Julio M., Economides K.D., et al. A luminal epithelial stem cell that is a cell of origin for prostate cancer. Nature 2009, 461:495-500.
45. Wyatt A.W., Mo F., Wang Y., Collins C.C. The diverse heterogeneity of molecular alterations in prostate cancer identified through next-generation sequencing. Asian J Androl 2013, 15:301-308.
46. Huss W.J., Gray D.R., Werdin E.S., Funkhouser W.K., Smith G.J. Evidence of pluripotent human prostate stem cells in a human prostate primary xenograft model. Prostate 2004, 60:77-90.
47. Rybak A.P., Ingram A.J., Tang D. Propagation of human prostate cancer stem-like cells occurs through EGFR-mediated ERK activation. PLOS ONE 2013, 8e61716.
48. Germann M., Wetterwald A., Guzmán-Ramirez N., et al. Stem-like cells with luminal progenitor phenotype survive castration in human prostate cancer. Stem Cells 2012, 30:1076-1086.
49. Bae K.M., Su Z., Frye C., et al. Expression of pluripotent stem cell reprogramming factors by prostate tumor initiating cells. J Urol 2010, 183:2045-2053.
50. Sotomayor P., Godoy A., Smith G.J., Huss W.J. Oct4A is expressed by a subpopulation of prostate neuroendocrine cells. Prostate 2009, 69:401-410.
51. Mani S.A., Guo W., Liao M.J., et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008, 133:704-715.
52. Nauseef J.T., Henry M.D. Epithelial-to-mesenchymal transition in prostate cancer: paradigm or puzzle?. Nat Rev Urol 2011, 8:428-439.
53. Cottard F., Asmane I., Erdmann E., Bergerat J.P., Kurtz J.E., Céraline J. Constitutively active androgen receptor variants upregulate expression of mesenchymal markers in prostate cancer cells. PLOS ONE 2013, 8e63466.
54. McKeithen D., Graham T., Chung L.W., Odero-Marah V. Snail transcription factor regulates neuroendocrine differentiation in LNCaP prostate cancer cells. Prostate 2010, 70:982-992.
55. Smith B.N., Odero-Marah V.A. The role of Snail in prostate cancer. Cell Adhes Migr 2012, 6:433-441.
56. Liu Y.N., Yin J.J., Abou-Kheir W., et al. MiR-1 and miR-200 inhibit EMT via Slug-dependent and tumorigenesis via Slug-independent mechanisms. Oncogene 2013, 32:296-306.
57. Zheng C., Yinghao S., Li J. MiR-221 expression affects invasion potential of human prostate carcinoma cell lines by targeting DVL2. Med Oncol 2012, 29:815-822.
58. Salvatori L., Caporuscio F., Verdina A., et al. Cell-to-cell signaling influences the fate of prostate cancer stem cells and their potential to generate more aggressive tumors. PLoS ONE 2012, 7e31467.
59. Berruti A., Dogliotti L., Mosca A., et al. Potential clinical value of circulating chromogranin A in patients with prostate carcinoma. Ann Oncol 2001, 12:153-157.
60. Angelsen A., Syversen U., Haugen O.A., Stridsberg M., Mjølnerød O.K., Waldum H.L. Neuroendocrine differentiation in carcinomas of the prostate: do neuroendocrine serum markers reflect immunohistochemical findings?. Prostate 1997, 30:1-6.
61. 111In]-labeled DTPA-D-[Phe1]-octreotide scintigraphy. Cancer Res 1995, 55:5805-5810.
62. Kalkner K.M., Acosta S., Thorsson O., et al. Octreotide scintigraphy and chromogranin A do not predict clinical response in patients with octreotide acetate-treated hormone-refractory prostate cancer. Prostate Cancer Prostatic Dis 2006, 9:92-98.
63. Gabriel M., Decristoforo C., Kendler D., et al. 68Ga-DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med 2007, 48:508-518.
64. De Vincentis G., Remediani S., Varvarigou A.D., et al. Role of 99mTc-bombesin scan in diagnosis and staging of prostate cancer. Cancer Biother Radiopharm 2004, 19:81-84.
65. Conteduca V., Zamarchi R., Rossi E., Condelli V., Troiani L., Aieta M. Circulating tumor cells: utopia or reality?. Future Oncol 2013, 9:1337-1352.
66. de Bono J.S., Scher H.I., Montgomery R.B. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 2008, 14:6302-6309.
67. Scher H.I., Jia X., de Bono J.S., et al. Circulating tumor cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol 2009, 10:233-239.
68. Chan F., Goodman O., Fink L., Vogelzang N.J., Pomerantz D., Khoury J.D. Dramatically elevated circulating tumor cell numbers in a patient with small cell neuroendocrine carcinoma of the prostate. Arch Pathol Lab Med 2010, 134:120-123.
69. Kani K., Malihi P.D., Jiang Y., et al. Anterior gradient 2 (AGR2): blood-based biomarker elevated in metastatic prostate cancer associated with the neuroendocrine phenotype. Prostate 2013, 73:306-315.
70. Berruti A., Mosca A., Porpiglia F., Chromogranin A., et al. expression in patients with hormone naïve prostate cancer predicts the development of hormone refractory disease. J Urol 2007, 178:838-843.
71. May M., Sieqsmund M., Hammermann F., Loy V., Gunia S. Prognostic significance of proliferation activity and neuroendocrine differentiation to predict treatment failure after radical prostatectomy. Scand J Urol Nephrol 2007, 41:375-381.
72. Berruti A., Mosca A., Tucci M., et al. Independent prognostic role of circulating chromogranin A in prostate cancer patients with hormone-refractory disease. Endocr Relat Cancer 2005, 12:109-117.
73. Taplin M.E., George D.J., Halabi S., et al. Prognostic significance of plasma chromogranin a levels in patients with hormone-refractory prostate cancer treated in cancer and leukemia Group B 9480 study. Urology 2005, 66:386-391.
74. Krauss D.J., Hayek S., Amin M., et al. Prognostic significance of neuroendocrine differentiation in patients with gleason score 8-10 prostate cancer treated with primary radiotherapy. Int J Radiat Oncol Biol Phys 2011, 81:119-125.
75. Puccetti L., Supuran C.T., Fasolo P.P., et al. Skewing towards neuroendocrine phenotype in high grade or high stage androgen-responsive primary prostate cancer. Eur Urol 2005, 48:215-221.
76. Nadal R., Schweizer M., Kryvenko O.N., Epstein J.I., Eisenberger M.A. Small cell carcinoma of the prostate. Nat Rev Urol 2014, 11:213-219.
77. Wu J.T., Astill M.E., Liu G.H., Stephenson R.A. Serum chromogranin a: early detection of hormonal resistance in prostate cancer patients. J Clin Lab Anal 1998, 12:20-25.
78. Burgio S.L., Conteduca V., Menna C., et al. Chromogranin A predicts outcome in prostate cancer patients treated with abiraterone. Endocr Relat Cancer 2014, 21:487-493.
79. Sciarra A., Monti S., Gentile V., et al. Variation in chromogranin A serum levels during intermittent versus continuous androgen deprivation therapy for prostate adenocarcinoma. Prostate 2003, 55:168-179.
80. Zaky Ahel M., Kovacic K., Kraljic I., Tarle M. Oral estramustine therapy in serum chromogranin A-positive stage D3 prostate cancer patients. Anticancer Res 2001, 21:1475-1479.
81. Papandreou C.N., Daliani D.D., Thall P.F., et al. Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small cell carcinoma of the prostate. J Clin Oncol 2002, 20:3072-3080.
82. Culine S., El Demery M., Lamy P.J., Iborra F., Avancès C., Pinguet F. Docetaxel and cisplatin in patients with metastatic androgen independent prostate cancer and circulating neuroendocrine markers. J Urol 2007, 178:844-848.
83. Loriot Y., Massard C., Gross-Goupil M., et al. Combining carboplatin and etoposide in docetaxel-pretreated patients with castration-resistant prostate cancer: a prospective study evaluating also neuroendocrine features. Ann Oncol 2009, 20:703-708.
84. Flechon A., Pouessel D., Ferlay C., et al. Phase II study of carboplatin and etoposide in patients with anaplastic progressive metastatic castration-resistant prostate cancer (mCRPC) with or without neuroendocrine differentiation: results of the French Genito-Urinary Tumor Group (GETUG) P01 trial. Ann Oncol 2011, 22:2476-2481.
85. Aparicio A.M., Harzstark A.L., Corn P.G., et al. Platinum-based chemotherapy for variant castrate-resistant prostate cancer. Clin Cancer Res 2013, 19:3621-3630.
86. Hansson J., Bjartell A., Gadaleanu V., Dizeyi N., Abrahamsson P.A. Expression of somatostatin receptor subtypes 2 and 4 in human benign prostatic hyperplasia and prostatic cancer. Prostate 2002, 53:50-59.
87. Msaouel P., Galanis E., Koutsilieris M. Somatostatin and somatostatin receptors: implications for neoplastic growth and cancer biology. Expert Opin Investig Drugs 2009, 18:1297-1316.
88. Berruti A., Dogliotti L., Mosca A., et al. Effects of the somatostatin analog lanreotide on the circulating levels of chromogranin-A, prostate-specific antigen, and insulin-like growth factor-1 in advanced prostate cancer patients. Prostate 2001, 47:205-211.
89. Mitsogiannis I.C., Skolarikos A., Deliveliotis C. Somatostatin analog lanreotide in the treatment of castration-resistant prostate cancer (CRPC). Expert Opin Pharmacother 2009, 10:493-501.
90. Koutsilieris M., Dimopoulos T., Milathianakis C., et al. Combination of somatostatin analogues and dexamethasone (antisurvival-factor concept) with luteinizing hormone-releasing hormone in androgen ablation-refractory prostate cancer with bone metastasis. BJU Int 2007, 100(Suppl. 2):60-62.
91. Dimopoulos M.A., Kiamouris C., Gika D., et al. Combination of LHRH analog with somatostatin analog and dexamethasone versus chemotherapy in hormone-refractory prostate cancer: a randomized phase II study. Urology 2004, 63:120-125.
92. Koutsilieris M., Bogdanos J., Milathianakis C., et al. Combination therapy using LHRH and somatostatin analogues plus dexamethasone in androgen ablation refractory prostate cancer patients with bone involvement: a bench to bedside approach. Expert Opin Investig Drugs 2006, 15:795-804.
93. Sciarra A., Bosman C., Monti G., et al. Somatostatin analogues and estrogens in the treatment of androgen ablation refractory prostate adenocarcinoma. J Urol 2004, 172:1775-1783.
94. Di Silverio F., Sciarra A. Combination therapy of ethinylestradiol and somatostatin analogue reintroduces objective clinical responses and decreases chromogranin a in patients with androgen ablation refractory prostate cancer. J Urol 2003, 170:1812-1816.
95. Cerulli C., Sciarra A., Salvatori G., Di Silverio F. Long-term response to combination therapy with estramustine and somatostatin analogue in a patient with androgen ablation-refractory prostate cancer. Urology 2004, 64:1231.e1-1231.e3.
96. Lo Nigro C., Maffi M., Fischel J.L., Formento P., Milano G., Merlano M. The combination of docetaxel and the somatostatin analogue lanreotide on androgen-independent docetaxel-resistant prostate cancer: experimental data. BJU Int 2008, 102:622-627.
97. Schmid H.A. Pasireotide (SOM230): development, mechanism of action and potential applications. Mol Cell Endocrinol 2008, 286:69-74.
98. Sansovini M., Severi S., Ambrosetti A., et al. Treatment with the radiolabelled somatostatin analog Lu-DOTATATE for advanced pancreatic neuroendocrine tumors. Neuroendocrinology 2013, 97:347-354.
99. Stangelberger A., Schally A.V., Varga J.L., et al. Inhibition of human androgen-independent PC-3 and DU-145 prostate cancers by antagonists of bombesin and growth hormone releasing hormone is linked to PKC, MAPK and c-jun intracellular signalling. Eur J Cancer 2005, 41:2735-2744.
100. Abdul M., Anezinis P.E., Logothetis C.J., Hoosein N.M. Growth inhibition of human prostatic carcinoma cell lines by serotonin antagonists. Anticancer Res 1994, 14:1215-1220.
101. Meulenbeld H.J., Bleuse J.P., Vinci E.M., et al. Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure. BJU Int 2013, 111:44-52.
102. Feng S., Agoulnik I.U., Truong A., et al. Suppression of relaxin receptor RXFP1 decreases prostate cancer growth and metastasis. Endocr Relat Cancer 2010, 17:1021-1033.
103. Burgio S.L., Fabbri F., Seymour I.J., Zoli W., Amadori D., De Giorgi U. Perspectives on mTOR inhibitors for castration-refractory prostate cancer. Curr Cancer Drug Targets 2012, 12:940-949.
104. Don A.S., Zheng X.F. Recent clinical trials of mTOR-targeted cancer therapies. Rev Recent Clin Trials 2011, 6:24-35.
105. Cortés M.A., Cariaga-Martinez A.E., Lobo M.V., et al. EGF promotes neuroendocrine-like differentiation of prostate cancer cells in the presence of LY294002 through increased ErbB2 expression independent of the phosphatidylinositol 3-kinase-AKT pathway. Carcinogenesis 2012, 33:1169-1177.
106. Hashimoto K., Masumori N., Tanaka T., et al. Zoledronic acid but not somatostatin analogs exerts anti-tumor effects in a model of murine prostatic neuroendocrine carcinoma of the development of castration-resistant prostate cancer. Prostate 2013, 73:500-511.
107. Knudsen K.E., Scher H.I. Starving the addiction: new opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res 2009, 15:4792-4798.
108. Sun Y., Wang B.E., Leong K.G., et al. Androgen deprivation causes epithelial-mesenchymal transition in the prostate: implications for androgen-deprivation therapy. Cancer Res 2012, 72:527-536.