TAK-441, a novel investigational smoothened antagonist, delays castration-resistant progression in prostate cancer by disrupting paracrine hedgehog signaling

International Journal of Cancer

Volumn 133, Issue 8, 2013, Pages 1955-1966

  Ibuki, Naokazu ^a   Ghaffari, Mazyar ^a,b   Pandey, Mitali ^a   Iu, Irene ^a   Fazli, Ladan ^a   Kashiwagi, Masahide ^c   Tojo, Hideaki ^c   Nakanishi, Osamu ^c   Gleave, Martin E ^a,b   Cox, Michael E ^a,b  

^a VANCOUVER GENERAL HOSPITAL   (Canada)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c TAKEDA PHARMACEUTICAL COMPANY LIMITED   (Japan)

Author keywords

hedgehog signaling; prostate cancer; small molecule inhibitor; smoothened

Indexed keywords

6 ETHYL N [1 (HYDROXYACETYL)PIPERIDIN 4 YL] 1 METHYL 4 OXO 5 (2 OXO 2 PHENYLETHYL) 3 (2,2,2 TRIFLUOROETHOXY) 4,5 DIHYDRO 1H PYRROLO[3,2 C]PYRIDINE 2 CARBOXAMIDE; ANTINEOPLASTIC AGENT; CYCLOPAMINE; PROTEIN PATCHED 1; SMOOTHENED PROTEIN; SONIC HEDGEHOG PROTEIN; TAK 441; TRANSCRIPTION FACTOR GLI1; TRANSCRIPTION FACTOR GLI2; UNCLASSIFIED DRUG;

ANDROGEN DEPRIVATION THERAPY; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CASTRATION RESISTANT PROSTATE CANCER; CELL VIABILITY; COHORT ANALYSIS; CONTROLLED STUDY; DOSE RESPONSE; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; MAJOR CLINICAL STUDY; MALE; MOUSE; NONHUMAN; PARACRINE SIGNALING; PRIORITY JOURNAL; PROTEIN EXPRESSION; UPREGULATION;

HEDGEHOG SIGNALING; PROSTATE CANCER; SMALL MOLECULE INHIBITOR; SMOOTHENED;

ANIMALS; ANTINEOPLASTIC AGENTS; CASTRATION; CELL LINE, TUMOR; CELL PROLIFERATION; DISEASE PROGRESSION; HEDGEHOG PROTEINS; HUMANS; MALE; MICE; MICE, NUDE; NEOPLASM TRANSPLANTATION; PARACRINE COMMUNICATION; PROSTATIC NEOPLASMS; PYRIDINES; PYRROLES; RECEPTORS, G-PROTEIN-COUPLED; TUMOR MICROENVIRONMENT; VERATRUM ALKALOIDS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84881547712     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.28193     Document Type: Article

References (56)

1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006; 56: 106-30.
2. Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 2012; 13: 983-92.
3. Scher HI, Fizazi K, Saad F, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012; 367: 1187-97.
4. Scher HI, Sawyers CL,. Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. J Clin Oncol 2005; 23: 8253-61.
5. Narita S, So A, Ettinger S, et al. GLI2 knockdown using an antisense oligonucleotide induces apoptosis and chemosensitizes cells to paclitaxel in androgen-independent prostate cancer. Clin Cancer Res 2008; 14: 5769-77.
6. Cohen MM, Jr., The hedgehog signaling network. Am J Med Genet A 2003; 15: 5-28.
7. Lum L, Beachy PA,. The Hedgehog response network: sensors, switches, and routers. Science 2004; 304: 1755-9.
8. Riobo NA, Saucy B, Dilizio C, et al. Activation of heterotrimeric G proteins by Smoothened. Proc Natl Acad Sci USA 2006; 103: 12607-12.
9. Berman DM, Karhadkar SS, Maitra A, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 2003; 425: 846-51.
10. Watkins DN, Berman DM, Burkholder SG, et al. Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer. Nature 2003; 422: 313-7.
11. Yauch RL, Gould SE, Scales SJ, et al. A paracrine requirement for hedgehog signalling in cancer. Nature 2008; 455: 406-10.
12. Pan Y, Bai CB, Joyner AL, et al. Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing its processing and degradation. Mol Cell Biol 2006; 26: 3365-77.
13. Fan H, Oro AE, Scott MP, et al. Induction of basal cell carcinoma features in transgenic human skin expressing Sonic Hedgehog. Nat Med 1997; 3: 788-92.
14. Sheng T, Li C, Zhang X, et al. Activation of the hedgehog pathway in advanced prostate cancer. Mol Cancer 2004; 3: 29.
15. Karhadkar SS, Bova GS, Abdallah N, et al. Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature 2004; 431: 707-12.
16. Sanchez P, Hernandez AM, Stecca B, et al. Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci USA 2004; 101: 12561-6.
17. Scales SJ, de Sauvage FJ,. Mechanisms of Hedgehog pathway activation in cancer and implications for therapy. Trends Pharmacol Sci 2009; 30: 303-12.
18. Teglund S, Toftgard R,. Hedgehog beyond medulloblastoma and basal cell carcinoma. Biochim Biophys Acta 2010; 2: 181-208.
19. Dennler S, Andre J, Alexaki I, et al. Induction of sonic hedgehog mediators by transforming growth factor-beta: Smad3-dependent activation of Gli2 and Gli1 expression in vitro and in vivo. Cancer Res 2007; 67: 6981-6.
20. Pasca di Magliano M, Sekine S, Ermilov A, et al. Hedgehog/Ras interactions regulate early stages of pancreatic cancer. Genes Dev 2006; 20: 3161-73.
21. Datta S, Datta MW,. Sonic Hedgehog signaling in advanced prostate cancer. Cell Mol Life Sci 2006; 63: 435-48.
22. Azoulay S, Terry S, Chimingqi M, et al. Comparative expression of Hedgehog ligands at different stages of prostate carcinoma progression. J Pathol 2008; 216: 460-70.
23. McKee CM, Xu D, Cao Y, et al. Protease nexin 1 inhibits hedgehog signaling in prostate adenocarcinoma. J Clin Invest 2012; 122: 4025-36.
24. Zhang J, Lipinski R, Shaw A, et al. Lack of demonstrable autocrine hedgehog signaling in human prostate cancer cell lines. J Urol 2007; 177: 1179-85.
25. Chen M, Tanner M, Levine AC, et al. Androgenic regulation of hedgehog signaling pathway components in prostate cancer cells. Cell Cycle 2009; 8: 149-57.
26. Fan L, Pepicelli CV, Dibble CC, et al. Hedgehog signaling promotes prostate xenograft tumor growth. Endocrinology 2004; 145: 3961-70.
27. Shigemura K, Huang WC, Li X, et al. Active sonic hedgehog signaling between androgen independent human prostate cancer cells and normal/benign but not cancer-Associated prostate stromal cells. Prostate 2011; 71: 1711-22.
28. Shaw A, Gipp J, Bushman W,. The Sonic Hedgehog pathway stimulates prostate tumor growth by paracrine signaling and recapitulates embryonic gene expression in tumor myofibroblasts. Oncogene 2009; 28: 4480-90.
29. Domenech M, Bjerregaard R, Bushman W, et al. Hedgehog signaling in myofibroblasts directly promotes prostate tumor cell growth. Integr Biol 2012; 4: 142-52.
30. Karlou M, Lu JF, Wu G, et al. Hedgehog signaling inhibition by the small molecule smoothened inhibitor GDC-0449 in the bone forming prostate cancer xenograft MDA PCa 118b. Prostate 2012; 27: 22517.
31. Ohashi T, Oguro Y, Tanaka T, et al. Discovery of the investigational drug TAK-441, a pyrrolo[3,2-c]pyridine derivative, as a highly potent and orally active hedgehog signaling inhibitor: modification of the core skeleton for improved solubility. Bioorg Med Chem 2012; 27: 27.
32. Leung SY, Jackson J, Miyake H, et al. Polymeric micellar paclitaxel phosphorylates Bcl-2 and induces apoptotic regression of androgen-independent LNCaP prostate tumors. Prostate 2000; 44: 156-63.
33. Tzelepi V, Karlou M, Wen S, et al. Expression of hedgehog pathway components in prostate carcinoma microenvironment: shifting the balance towards autocrine signalling. Histopathology 2011; 58: 1037-47.
34. Shaw G, Prowse DM,. Inhibition of androgen-independent prostate cancer cell growth is enhanced by combination therapy targeting Hedgehog and ErbB signalling. Cancer Cell Int 2008; 8: 1475-2867.
35. Kiyama S, Morrison K, Zellweger T, et al. Castration-induced increases in insulin-like growth factor-binding protein 2 promotes proliferation of androgen-independent human prostate LNCaP tumors. Cancer Res 2003; 63: 3575-84.
36. Pietsch T, Waha A, Koch A, et al. Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res 1997; 57: 2085-8.
37. Epstein EH,. Basal cell carcinomas: attack of the hedgehog. Nat Rev Cancer 2008; 8: 743-54.
38. Heller E, Hurchla MA, Xiang J, et al. Hedgehog signaling inhibition blocks growth of resistant tumors through effects on tumor microenvironment. Cancer Res 2012; 72: 897-907.
39. Podlasek CA, Barnett DH, Clemens JQ, et al. Prostate development requires Sonic hedgehog expressed by the urogenital sinus epithelium. Dev Biol 1999; 209: 28-39.
40. Freestone SH, Marker P, Grace OC, et al. Sonic hedgehog regulates prostatic growth and epithelial differentiation. Dev Biol 2003; 264: 352-62.
41. Pu Y, Huang L, Prins GS,. Sonic hedgehog-patched Gli signaling in the developing rat prostate gland: lobe-specific suppression by neonatal estrogens reduces ductal growth and branching. Dev Biol 2004; 273: 257-75.
42. Berman DM, Desai N, Wang X, et al. Roles for Hedgehog signaling in androgen production and prostate ductal morphogenesis. Dev Biol 2004; 267: 387-98.
43. Sirab N, Terry S, Giton F, et al. Androgens regulate Hedgehog signalling and proliferation in androgen-dependent prostate cells. Int J Cancer 2012; 131: 1297-306.
44. Levitt RJ, Zhao Y, Blouin MJ, et al. The hedgehog pathway inhibitor cyclopamine increases levels of p27, and decreases both expression of IGF-II and activation of Akt in PC-3 prostate cancer cells. Cancer Lett 2007; 255: 300-6.
45. Zhang X, Harrington N, Moraes RC, et al. Cyclopamine inhibition of human breast cancer cell growth independent of Smoothened (Smo). Breast Cancer Res Treat 2009; 115: 505-21.
46. Gupta S, Takebe N, Lorusso P,. Targeting the Hedgehog pathway in cancer. Ther Adv Med Oncol 2010; 2: 237-50.
47. Tremblay MR, Nesler M, Weatherhead R, et al. Recent patents for Hedgehog pathway inhibitors for the treatment of malignancy. Expert Opin Ther Pat 2009; 19: 1039-56.
48. Yun JI, Kim HR, Park H, et al. Small molecule inhibitors of the hedgehog signaling pathway for the treatment of cancer. Arch Pharm Res 2012; 35: 1317-33.
49. Von Hoff DD, LoRusso PM, Rudin CM, et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 2009; 361: 1164-72.
50. Rudin CM, Hann CL, Laterra J, et al. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 2009; 361: 1173-8.
51. Slusarz A, Shenouda NS, Sakla MS, et al. Common botanical compounds inhibit the hedgehog signaling pathway in prostate cancer. Cancer Res 2010; 70: 3382-90.
52. Attardi BJ, Burgenson J, Hild SA, et al. Steroid hormonal regulation of growth, prostate specific antigen secretion, and transcription mediated by the mutated androgen receptor in CWR22Rv1 human prostate carcinoma cells. Mol Cell Endocrinol 2004; 222: 121-32.
53. Antonarakis ES, Heath EI, Smith DC, et al. Repurposing itraconazole as a treatment for advanced prostate cancer: a noncomparative randomized phase II trial in men with metastatic castration-resistant prostate cancer. Oncologist 2013; 18: 163-73.
54. Tian H, Callahan CA, DuPree KJ, et al. Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proc Natl Acad Sci USA 2009; 106: 4254-9.
55. Beachy PA, Karhadkar SS, Berman DM,. Tissue repair and stem cell renewal in carcinogenesis. Nature 2004; 432: 324-31.
56. Chen W, Tang T, Eastham-Anderson J, et al. Canonical hedgehog signaling augments tumor angiogenesis by induction of VEGF-A in stromal perivascular cells. Proc Natl Acad Sci USA 2011; 108: 9589-94.