Second-generation HSP90 inhibitor onalespib blocks mRNA splicing of androgen receptor variant 7 in prostate cancer cells

Cancer Research

Volumn 76, Issue 9, 2016, Pages 2731-2742

  Ferraldeschi, Roberta ^a,b   Welti, Jonathan ^a   Powers, Marissa V ^a   Yuan, Wei ^a   Smyth, Tomoko ^c   Seed, George ^a   Riisnaes, Ruth ^a   Hedayat, Somaieh ^a   Wang, Hannah ^a   Crespo, Mateus ^a   Rodrigues, Daniel Nava ^a   Figueiredo, Ines ^a   Miranda, Susana ^a   Carreira, Suzanne ^a   Lyons, John F ^c   Sharp, Swee ^a   Plymate, Stephen R ^d   Attard, Gerhardt ^a,b   Wallis, Nicola ^c   Workman, Paul ^a   De Bono, Johann S ^a,b   more..

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^c ASTEX PHARMACEUTICALS   (United Kingdom)

^d UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALVESPIMYCIN; ANDROGEN RECEPTOR; ANDROGEN RECEPTOR VARIANT 7; HEAT SHOCK PROTEIN 90; MESSENGER RNA; ONALESPIB; RETASPIMYCIN; UNCLASSIFIED DRUG; (2,4-DIHYDROXY-5-ISOPROPYLPHENYL)-(5-(4-METHYLPIPERAZIN-1-YLMETHYL)-1,3-DIHYDROISOINDOL-2-YL)METHANONE; AR PROTEIN, HUMAN; BENZAMIDE DERIVATIVE; ISOINDOLE DERIVATIVE;

ANDROGEN RECEPTOR VARIANT 7 GENE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BINDING AFFINITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG MECHANISM; GENE EXPRESSION; MALE; MITOSIS INHIBITION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER CELL LINE; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; RNA SPLICING; SOLID TUMOR; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; DRUG RESISTANCE; DRUG SCREENING; GENETICS; HUMAN; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; METABOLISM; PATHOLOGY; POLYMERASE CHAIN REACTION; PROSTATE TUMOR; TUMOR CELL LINE; WESTERN BLOTTING;

ANIMALS; BENZAMIDES; BLOTTING, WESTERN; CELL LINE, TUMOR; DRUG RESISTANCE, NEOPLASM; HSP90 HEAT-SHOCK PROTEINS; HUMANS; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; ISOINDOLES; MALE; MICE; POLYMERASE CHAIN REACTION; PROSTATIC NEOPLASMS; RECEPTORS, ANDROGEN; RNA SPLICING; RNA, MESSENGER; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84969627173     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-15-2186     Document Type: Article

References (55)

1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30.
2. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, MillerK, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 2012;367:1187-97.
3. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011;364:1995-2005.
4. Ware KE, Garcia-Blanco MA, Armstrong AJ,DehmSM. Biologic and clinical significance of androgen receptor variants in castration resistant prostate cancer. Endocr Relat Cancer 2014;21:T87-T103.
5. Guo Z, Yang X, Sun F, Jiang R, Linn DE, Chen H, et al. A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth. Cancer Res 2009; 69:2305-13.
6. Hu R, Dunn TA, Wei S, Isharwal S, Veltri RW, Humphreys E, et al. Ligandindependent androgen receptor variants derived from splicing of cryptic exons signify hormone-refractory prostate cancer. Cancer Res 2009;69:16-22.
7. Li Y, Chan SC, Brand LJ, Hwang TH, Silverstein KA, Dehm SM. Androgen receptor splice variants mediate enzalutamide resistance in castrationresistant prostate cancer cell lines. Cancer Res 2013;73:483-9.
8. Hornberg E, Ylitalo EB, Crnalic S, Antti H, Stattin P, Widmark A, et al. Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival. PLoS One 2011;6:e19059.
9. Sun S, Sprenger CC, Vessella RL, Haugk K, Soriano K, Mostaghel EA, et al. Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. J Clin Invest 2010;120:2715-30.
10. Zhang X, Morrissey C, Sun S, Ketchandji M, Nelson PS, True LD, et al. Androgen receptor variants occur frequently in castration resistant prostate cancer metastases. PLoS One 2011;6:e27970.
11. Hu R, Lu C, Mostaghel EA, Yegnasubramanian S, Gurel M, Tannahill C, et al. Distinct transcriptional programs mediated by the ligand-dependent full-length androgen receptor and its splice variants in castration-resistant prostate cancer. Cancer Res 2012;72:3457-62.
12. Mostaghel EA, Marck BT, Plymate SR, Vessella RL, Balk S, Matsumoto AM, et al. Resistance to CYP17A1 inhibition with abiraterone in castrationresistant prostate cancer: induction of steroidogenesis and androgen receptor splice variants. Clin Cancer Res 2011;17:5913-25.
13. Yu Z, Chen S, Sowalsky AG, Voznesensky O, Mostaghel EA, Nelson PS, et al. Rapid induction of androgen receptor splice variants by androgen deprivation in prostate cancer. Clin Cancer Res 2014;20:1590-600.
14. Cao B, Qi Y, Zhang G, Xu D, Zhan Y, Alvarez X, et al. Androgen receptor splice variants activating the full-length receptor inmediating resistance to androgen-directed therapy. Oncotarget 2014;5:1646-56.
15. Robinson D, Van Allen EM, Wu YM, Schultz N, Lonigro RJ, Mosquera JM, et al. Integrative clinical genomics of advanced prostate cancer. Cell 2015;161:1215-28.
16. Chan SC, Selth LA, Li Y, Nyquist MD, Miao L, Bradner JE, et al. Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Res 2015;43:5880-97.
17. Efstathiou E, Titus M, Wen S, Hoang A, Karlou M, Ashe R, et al. Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol 2014;67:53-60.
18. Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, et al. ARV7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 2014;371:1028-38.
19. Georget V, Terouanne B, Nicolas JC, Sultan C. Mechanism of antiandrogen action: key role of hsp90 in conformational change and transcriptional activity of the androgen receptor. Biochemistry 2002; 41:11824-31.
20. Vanaja DK, Mitchell SH, Toft DO, Young CYF. Effect of geldanamycin on androgen receptor function and stability. Cell Stress Chaperones 2002;7:55-64.
21. Kirschke E, Goswami D, Southworth D, Griffin PR, Agard DA. Glucocorticoid receptor function regulated by coordinated action of the Hsp90 and Hsp70 chaperone cycles. Cell 2014;157:1685-97.
22. Hernandez MP, Chadli A, Toft DO. HSP40 binding is the first step in the HSP90 chaperoning pathway for the progesterone receptor. J Biol Chem 2002;277:11873-81.
23. Smith DF, Toft DO. Minireview: the intersection of steroid receptors with molecular chaperones: observations and questions. Mol Endocrinol 2008;22:2229-40.
24. Saporita AJ, Ai JK, Wang Z. The Hsp90 inhibitor, 17-AAG, prevents the ligand-independent nuclear localization of androgen receptor in refractory prostate cancer cells. Prostate 2007;67:509-20.
25. Solit DB, Zheng FZF, Drobnjak M, Munster PN, Higgins B, Verbel D, et al. 17-allylamino-17-demethoxygeldanamycin induces the degradation of androgen receptor and HER-2/neu and inhibits the growth of prostate cancer xenografts. Clin Cancer Res 2002;8:986-93.
26. Lamoureux F, Thomas C, Yin MJ, Kuruma H, Fazli L, Gleave ME, et al. A novel HSP90 inhibitor delays castrate-resistant prostate cancer without altering serum PSA levels and inhibits osteoclastogenesis. Clin Cancer Res 2011;17:2301-13.
27. O'Malley KJ, Langmann G, Ai J, Ramos-Garcia R, Vessella RL, Wang Z. Hsp90 inhibitor 17-AAG inhibits progression of LuCaP35 xenograft prostate tumors to castration resistance. Prostate 2012;72:1117-23.
28. Dehm SM, Schmidt LJ, Heemers HV, Vessella RL, Tindall DJ. Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res 2008;68:5469-77.
29. Gillis JL, Selth LA, Centenera MM, Townley SL, Sun S, Plymate SR, et al. Constitutively-active androgen receptor variants function independently of the HSP90 chaperone but do not confer resistance to HSP90 inhibitors. Oncotarget 2013;4:691-704.
30. Neckers L, Workman P. Hsp90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res 2012;18:64-76.
31. Woodhead AJ, Angove H, Carr MG, ChessariG, Congreve M, Coyle JE, et al. Discovery of (2,4-dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydrois oindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design. J Med Chem 2010;53:5956-69.
32. Kelland LR, Sharp SY, Rogers PM, Myers TG, Workman P. DT-Diaphorase expression and tumor cell sensitivity to 17-allylamino, 17-demethoxygeldanamycin, an inhibitor of heat shock protein 90. J Natl Cancer Inst 1999;91:1940-9.
33. Hostein I, Robertson D, DiStefano F, Workman P, Clarke PA. Inhibition of signal transduction by the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin results in cytostasis and apoptosis. Cancer Res 2001; 61:4003-9.
34. Richards J, Lim AC, Hay CW, Taylor AE, Wingate A, Nowakowska K, et al. Interactions of abiraterone, eplerenone, and prednisolone with wild-type and mutant androgen receptor: a rationale for increasing abiraterone exposure or combining with MDV3100. Cancer Res 2012;72:2176-82.
35. Graham B, Curry J, Smyth T, Fazal L, Feltell R, Harada I, et al. The heat shock protein 90 inhibitor, AT13387, displays a long duration of action in vitro and in vivo in non-small cell lung cancer. Cancer Sci 2012;103:522-7.
36. Shen S, Park JW, Huang J, Dittmar KA, Lu ZX, Zhou Q, et al. MATS: a Bayesian framework for flexible detection of differential alternative splicing from RNA-Seq data. Nucleic Acids Res 2012;40:e61.
37. Banerji U, Walton M, Raynaud F, Grimshaw R, Kelland L, Valenti M, et al. Pharmacokinetic-pharmacodynamic relationships for the heat shock protein 90 molecular chaperone inhibitor 17-allylamino, 17-demethoxygeldanamycin in human ovarian cancer xenograft models. Clin Cancer Res 2005;11:7023-32.
38. Gaspar N, Sharp SY, Pacey S, Jones C, Walton M, Vassal G, et al. Acquired Resistance to 17-Allylamino-17-Demethoxygeldanamycin (17-AAG, Tanespimycin) in Glioblastoma Cells. Cancer Res 2009;69:1966-75.
39. Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci U S A 1994;91:8324-8.
40. Prescott J, Coetzee GA. Molecular chaperones throughout the life cycle of the androgen receptor. Cancer Lett 2006;231:12-9.
41. de Billy E, Travers J, Workman P. Shock about heat shock in cancer. Oncotarget 2012;3:741-3.
42. Shalgi R, Hurt JA, Lindquist S, Burge CB. Widespread inhibition of posttranscriptional splicing shapes the cellular transcriptome following heat shock. Cell Rep 2014;7:1362-70.
43. Shin C, Feng Y, Manley JL. Dephosphorylated SRp38 acts as a splicing repressor in response to heat shock. Nature 2004;427:553-8.
44. Biamonti G, Caceres JF. Cellular stress and RNA splicing. Trends Biochem Sci 2009;34:146-53.
45. Liu LL, Xie N, Sun S, Plymate S, Mostaghel E, Dong X. Mechanisms of the androgen receptor splicing in prostate cancer cells. Oncogene 2014;33: 3140-50.
46. Long JC, Caceres JF. The SR protein family of splicing factors: master regulators of gene expression. Biochem J 2009;417:15-27.
47. Zhong XY, Ding JH, Adams JA, Ghosh G, Fu XD. Regulation of SR protein phosphorylation and alternative splicing by modulating kinetic interactions of SRPK1 with molecular chaperones. Genes Dev 2009;23:482-95.
48. Lynch KW. Regulation of alternative splicing by signal transduction pathways. Adv Exp Med Biol 2007;623:161-74.
49. Fu XD, Ares MJr. Context-dependent control of alternative splicing by RNAbinding proteins. Nat Rev Genet 2014;15:689-701.
50. Blaustein M, Pelisch F, Tanos T, Munoz MJ, Wengier D, Quadrana L, et al. Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT. Nat Struct Mol Biol 2005;12:1037-44.
51. Zhou Z, Qiu J, Liu W, Zhou Y, Plocinik RM, Li H, et al. The Akt-SRPK-SR axis constitutes a major pathway in transducing EGF signaling to regulate alternative splicing in the nucleus. Mol Cell 2012;47:422-33.
52. Shafi AA, Cox MB, Weigel NL. Androgen receptor splice variants are resistant to inhibitors of Hsp90 and FKBP52, which alter androgen receptor activity and expression. Steroids 2013;78:548-54.
53. Ramanathan RK, Egorin MJ, Erlichman C, Remick SC, Ramalingam SS, Naret C, et al. Phase I pharmacokinetic and pharmacodynamic study of 17-dimethylaminoethylamino-17-demethoxygeldanamycin, an inhibitor of heat-shock protein 90, in patients with advanced solid tumors. JClin Oncol 2010;28:1520-6.
54. Wang Y, Trepel JB, Neckers LM, Giaccone G. STA-9090, a small-molecule Hsp90 inhibitor for the potential treatment of cancer. Curr Opin Investig Drugs 2010;11:1466-76.
55. Ferraldeschi R SS, Hussain S, et al. A Phase 1/2 study of AT13387, a heat shock protein 90 (Hsp90) inhibitor in combination with abiraterone acetate (AA) and prednisone (P) in patients (pts) with castration-resistant prostate cancer (mCRPC) no longer responding to AA. Ann Oncol 2014;25: iv255-iv279.