Targeting AKT/mTOR and ERK MAPK signaling inhibits hormone-refractory prostate cancer in a preclinical mouse model

Journal of Clinical Investigation

Volumn 118, Issue 9, 2008, Pages 3051-3064

  Kinkade, Carolyn Waugh ^a   Castillo Martin, Mireia ^a   Puzio Kuter, Anna ^a   Yan, Jun ^a   Foster, Thomas H ^b   Gao, Hui ^c   Sun, Yvonne ^c   Ouyang, Xuesong ^c   Gerald, William L ^d   Cordon Cardo, Carlos ^a   Abate Shen, Cory ^a,c  

^a Columbia University College of Physicians and Surgeons ^*  (United States)

^b Urologische Klinik Universitatsspital Basel   (Switzerland)

^c RUTGERS UNIVERSITY   (United States)

^d MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIM PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; N (2,3 DIHYDROXYPROPOXY) 3,4 DIFLUORO 2 (2 FLUORO 4 IODOANILINO)BENZAMIDE; PROTEIN KINASE B; RAPAMYCIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER CELL CULTURE; CANCER GROWTH; CANCER INHIBITION; CANCER TISSUE; CARCINOGENICITY; CELL PROLIFERATION; COMBINATION CHEMOTHERAPY; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENTIATION; DRUG TARGETING; EMBRYO; ENZYME INHIBITION; EXPERIMENTAL MODEL; EXPERIMENTAL MOUSE; GENETIC ENGINEERING; HUMAN; HUMAN TISSUE; MALE; MICROARRAY ANALYSIS; MONOTHERAPY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; PROTEIN EXPRESSION; PROTEIN TARGETING; RAT; SIGNAL TRANSDUCTION; UPREGULATION;

ANIMALS; ANTINEOPLASTIC AGENTS; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; HORMONES; HUMANS; MALE; MAP KINASE SIGNALING SYSTEM; MICE; MODELS, BIOLOGICAL; PROSTATIC NEOPLASMS; PROTEIN KINASES; PROTO-ONCOGENE PROTEINS C-AKT;

EID: 51349111250     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI34764     Document Type: Article

References (49)

1. DeMarzo, A.M., Nelson, W.G., Isaacs, W.B., and Epstein, J.I. 2003. Pathological and molecular aspects of prostate cancer. Lancet. 361:955-964.
2. Gelmann, E.P. 2002. Molecular biology of the androgen receptor. J. Clin. Oncol. 20:3001-3015.
3. Scher, H.I., and Sawyers, C.L. 2005. Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. J. Clin. Oncol. 23:8253-8261.
4. Petrylak, D.P. 2007. New paradigms for advanced prostate cancer. Rev. Urol. 9(Suppl. 2):S3-S12.
5. Pienta, K.J., and Smith, D.C. 2005. Advances in prostate cancer chemotherapy: a new era begins. CA Cancer J. Clin. 55:300-318; quiz 323-305.
6. Berry, W.R. 2005. The evolving role of chemotherapy in androgen-independent (hormone-refractory) prostate cancer. Urology. 65(6 Suppl.):2-7.
7. Petrylak, D.P. 2005. The current role of chemotherapy in metastatic hormone-refractory prostate cancer. Urology. 65(5 Suppl.):3-7; discussion 7-8.
8. Malik, S.N., et al. 2002. Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer. Clin. Cancer Res. 8:1168-1171.
9. McMenamin, M.E., et al. 1999. Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res. 59:4291-4296.
10. Kremer, C.L., et al. 2006. Expression of mTOR signaling pathway markers in prostate cancer progression. Prostate. 66:1203-1212.
11. Paweletz, C.P., et al. 2001. Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front. Oncogene. 20:1981-1989.
12. Gioeli, D. 2005. Signal transduction in prostate cancer progression. Clin. Sci. (Lond.). 108:293-308.
13. Gioeli, D., Mandell, J.W., Petroni, G.R., Frierson, H.F., Jr., and Weber, M.J. 1999. Activation of mitogen-activated protein kinase associated with prostate cancer progression. Cancer Res. 59:279-284.
14. Abreu-Martin, M.T., Chari, A., Palladino, A.A., Craft, N.A., and Sawyers, C.L. 1999. Mitogen-activated protein kinase kinase kinase 1 activates androgen receptor-dependent transcription and apoptosis in prostate cancer. Mol. Cell. Biol. 19:5143-5154.
15. Gao, H., et al. 2006. Combinatorial activities of Akt and B-Raf/Erk signaling in a mouse model of androgen-independent prostate cancer. Proc. Natl. Acad. Sci. U. S. A. 103:14477-14482.
16. Uzgare, A.R., and Isaacs, J.T. 2004. Enhanced redundancy in Akt and mitogen-activated protein kinase-induced survival of malignant versus normal prostate epithelial cells. Cancer Res. 64:6190-6199.
17. Abate-Shen, C., et al. 2003. Nkx3.1; Pten mutant mice develop invasive prostate adenocarcinoma and lymph node metastases. Cancer Res. 63:3886-3890.
18. Kim, M.J., et al. 2002. Cooperativity of Nkx3.1 and Pten loss of function in a mouse model of prostate carcinogenesis. Proc. Natl. Acad. Sci. U. S. A. 99:2884-2889.
19. Gao, H., et al. 2004. A critical role for p27kip1 gene dosage in a mouse model of prostate carcinogenesis. Proc. Natl. Acad. Sci. U. S. A. 101:17204-17209.
20. Kuzmichev, A., et al. 2005. Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation. Proc. Natl. Acad. Sci. U. S. A. 102:1859-1864.
21. Ouyang, X., et al. 2008. Activator protein-1 transcription factors are associated with progression and recurrence of prostate cancer. Cancer Res. 68:2132-2144.
22. Sebolt-Leopold, J.S., and Herrera, R. 2004. Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat Rev Cancer 4:937-947.
23. Kohno, M., and Pouyssegur, J. 2006. Targeting the ERK signaling pathway in cancer therapy. Ann Med. 38:200-211.
24. Solit, D.B., et al. 2006. BRAF mutation predicts sensitivity to MEK inhibition. Nature. 439:358-362.
25. Hay, N., and Sonenberg, N. 2004. Upstream and downstream of mTOR. Genes Dev. 18:1926-1945.
26. Skeen, J.E., et al. 2006. Akt deficiency impairs normal cell proliferation and suppresses oncogenesis in a p53-independent and mTORC1-dependent manner. Cancer Cell. 10:269-280.
27. Sawyers, C.L. 2003. Will mTOR inhibitors make it as cancer drugs? Cancer Cell. 4:343-348.
28. Fan, Q.W., et al. 2007. A dual phosphoinositide-3-kinase alpha/mTOR inhibitor cooperates with blockade of epidermal growth factor receptor in PTEN-mutant glioma. Cancer Res. 67:7960-7965.
29. Neshat, M.S., et al. 2001. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc. Natl. Acad. Sci. U. S. A. 98:10314-10319.
30. +/- mice. Proc. Natl. Acad. Sci. U. S. A. 98:10320-10325.
31. Kwon, C.H., Zhu, X., Zhang, J., and Baker, S.J. 2003. mTor is required for hypertrophy of Pten-deficient neuronal soma in vivo. Proc. Natl. Acad. Sci. U. S. A. 100:12923-12928.
32. Majumder, P.K., et al. 2004. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat. Med. 10:594-601.
33. Brown, A.P., Carlson, T.C., Loi, C.M., and Graziano, M.J. 2007. Pharmacodynamic and toxicokinetic evaluation of the novel MEK inhibitor, PD0325901, in the rat following oral and intravenous administration. Cancer Chemother. Pharmacol. 59:671-679.
34. Chou, T.C., and Talalay, P. 1984. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regul. 22:27-55.
35. Gelinas, C., and White, E. 2005. BH3-only proteins in control: specificity regulates MCL-1 and BAK-mediated apoptosis. Genes Dev. 19:1263-1268.
36. White, E. 2006. Mechanisms of apoptosis regulation by viral oncogenes in infection and tumorigenesis. Cell Death Differ. 13:1371-1377.
37. Tan, T.T., et al. 2005. Key roles of BIM-driven apoptosis in epithelial tumors and rational chemotherapy. Cancer Cell. 7:227-238.
38. Petrylak, D.P. 2005. Chemotherapy for androgen-independent prostate cancer. World J. Urol. 23:10-13.
39. Druker, B.J., et al. 2001. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N. Engl. J. Med. 344:1038-1042.
40. Gorre, M.E., et al. 2001. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 293:876-880.
41. Abate-Shen, C. 2006. A new generation of mouse models of cancer for translational research. Clin. Cancer Res. 12:5274-5276.
42. Carver, B.S., and Pandolfi, P.P. 2006. Mouse modeling in oncologic preclinical and translational research. Clin. Cancer Res. 12:5305-5311.
43. Fomchenko, E.I., and Holland, E.C. 2006. Mouse models of brain tumors and their applications in preclinical trials. Clin. Cancer Res. 12:5288-5297.
44. Olive, K.P., and Tuveson, D.A. 2006. The use of targeted mouse models for preclinical testing of novel cancer therapeutics. Clin. Cancer Res. 12:5277-5287.
45. Carracedo, A., et al. 2008. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J. Clin. Invest. 118:3065-3074.
46. Xu, Y., Chen, S.Y., Ross, K.N., and Balk, S.P. 2006. Androgens induce prostate cancer cell proliferation through mammalian target of rapamycin activation and post-transcriptional increases in cyclin D proteins. Cancer Res. 66:7783-7792.
47. Stommel, J.M., et al. 2007. Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. Science. 318:287-290.
48. Shah, N.P., et al. 2007. Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency. J. Clin. Invest. 117:2562-2569.
49. Bhatia-Gaur, R., et al. 1999. Roles for Nkx3.1 in prostate development and cancer. Genes Dev. 13:966-977.