Receptor-targeted therapy of human experimental urinary bladder cancers with cytotoxic LH-RH analog AN-152 (AEZS-108)

Oncotarget

Volumn 3, Issue 7, 2012, Pages 686-699

  Szepeshazi, Karoly ^a,b   Schally, Andrew V ^a,b,c   Keller, Gunhild ^d   Block, Norman L ^a,b,c   Benten, Daniel ^d   Halmos, Gabor ^a,b,c,e   Szalontay, Luca ^a,b   Vidaurre, Irving ^a,b   Jaszberenyi, Miklos ^a,b,c   Rick, Ferenc G ^a,b,c  

^a VETERANS AFFAIRS MEDICAL CENTER   (United States)

^b South Florida VA Foundation for Research and Education   (United States)

^c UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^e UNIVERSITY OF DEBRECEN   (Hungary)

Author keywords

Cytotoxic; Doxorubicin; LH RH receptor; Targeted therapy; Urinary bladder; Urothelial cancer

Indexed keywords

CETRORELIX; DOXORUBICIN; GONADORELIN ANTAGONIST; GONADORELIN RECEPTOR; ZOPTARELIN DOXORUBICIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BLADDER CANCER; CANCER CELL CULTURE; CANCER COMBINATION CHEMOTHERAPY; CANCER INHIBITION; CANCER RESISTANCE; CLINICAL ARTICLE; CONTROLLED STUDY; FEMALE; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; MOLECULAR MODEL; MOUSE; MULTIDRUG RESISTANCE; NONHUMAN; POLYMERASE CHAIN REACTION; PROTEIN EXPRESSION; RECEPTOR AFFINITY; WESTERN BLOTTING;

EID: 84868626417     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.546     Document Type: Article

References (56)

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90.
2. Hollenbeck BK, Ye Z, Dunn RL, Montie JE and Birkmeyer JD. Provider treatment intensity and outcomes for patients with early-stage bladder cancer. J Natl Cancer Inst. 2009; 101(8):571-580.
3. Yagoda A. (1981). Chemotherapy of advanced bladder cancer. Progress in Cancer Reseach and Therapy: Raven Press, New York), pp. pp 251-260.
4. Citrin DL, Hogan TF and Davis TE. A study of cyclophosphamide, adriamycin, cis-platinum, and methotrexate in advanced transitional cell carcinoma of the urinary tract. Cancer. 1983; 51(1):1-4.
5. Loehrer PJ, Sr., Einhorn LH, Elson PJ, Crawford ED, Kuebler P, Tannock I, Raghavan D, Stuart-Harris R, Sarosdy MF, Lowe BA and et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1992; 10(7):1066-1073.
6. Tada Y, Wada M, Migita T, Nagayama J, Hinoshita E, Mochida Y, Maehara Y, Tsuneyoshi M, Kuwano M and Naito S. Increased expression of multidrug resistance-associated proteins in bladder cancer during clinical course and drug resistance to doxorubicin. Int J Cancer. 2002; 98(4):630-635.
7. Sternberg CN, de Mulder PH, Schornagel JH, Theodore C, Fossa SD, van Oosterom AT, Witjes F, Spina M, van Groeningen CJ, de Balincourt C and Collette L. Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European Organization for Research and Treatment of Cancer Protocol no. 30924. J Clin Oncol. 2001; 19(10):2638-2646.
8. Bamias A, Aravantinos G, Deliveliotis C, Bafaloukos D, Kalofonos C, Xiros N, Zervas A, Mitropoulos D, Samantas E, Pectasides D, Papakostas P, Gika D, Kourousis C, Koutras A, Papadimitriou C, Bamias C, et al. Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group. J Clin Oncol. 2004; 22(2):220-228.
9. Costantini C and Millard F. Update on chemotherapy in the treatment of urothelial carcinoma. ScientificWorldJournal. 2011; 11:1981-1994.
10. Black PC and Dinney CP. Growth factors and receptors as prognostic markers in urothelial carcinoma. Curr Urol Rep. 2008; 9(1):55-61.
11. Vom Dorp F, Borgermann C, Rose A, Becker M and Rubben H. [Targeted therapy for metastatic bladder cancer]. Urologe A. 2008; 47(10):1311-1314.
12. Bellmunt J, Albiol S, Suarez C and Albanell J. Optimizing therapeutic strategies in advanced bladder cancer: update on chemotherapy and the role of targeted agents. Crit Rev Oncol Hematol. 2009; 69(3):211-222.
13. Zieger K. High throughput molecular diagnostics in bladder cancer - on the brink of clinical utility. Mol Oncol. 2008; 1(4):384-394.
14. Siejka A, Barabutis N and Schally AV. GHRH antagonist MZ-5-156 increases the expression of AMPK in A549 lung cancer cells. Cell Cycle. 2011; 10(21):3714-3718.
15. Barabutis N and Schally AV. Growth hormone-releasing hormone: extrapituitary effects in physiology and pathology. Cell Cycle. 2010; 9(20):4110-4116.
16. Hohla F and Schally AV. Targeting gastrin releasing peptide receptors: New options for the therapy and diagnosis of cancer. Cell Cycle. 2010; 9(9):1738-1741.
17. Schally AV and Nagy A. Chemotherapy targeted to cancers through tumoral hormone receptors. Trends Endocrinol Metab. 2004; 15(7):300-310.
18. Schally AV, Engel JB, Emons G, Block NL and Pinski J. Use of analogs of peptide hormones conjugated to cytotoxic radicals for chemotherapy targeted to receptors on tumors. Curr Drug Deliv. 2011; 8(1):11-25.
19. Schally AV and Halmos G. (2012). Targeting to peptide receptors. In: Kratz S, Steinhagen, ed. Drug delivery in Oncology From Basic Research to Cancer Therapy: Wiley - VCH), pp. 1219-1261.
20. Halmos G, Arencibia JM, Schally AV, Davis R and Bostwick DG. High incidence of receptors for luteinizing hormone-releasing hormone (LHRH) and LHRH receptor gene expression in human prostate cancers. J Urol. 2000; 163(2):623-629.
21. Keller G, Schally AV, Gaiser T, Nagy A, Baker B, Halmos G and Engel JB. Receptors for luteinizing hormone releasing hormone (LHRH) expressed in human non-Hodgkin's lymphomas can be targeted for therapy with the cytotoxic LHRH analogue AN-207. Eur J Cancer. 2005; 41(14):2196-2202.
22. Keller G, Schally AV, Gaiser T, Nagy A, Baker B, Halmos G and Engel JB. Receptors for luteinizing hormone releasing hormone expressed on human renal cell carcinomas can be used for targeted chemotherapy with cytotoxic luteinizing hormone releasing hormone analogues. Clin Cancer Res. 2005; 11(15):5549-5557.
23. Keller G, Schally AV, Gaiser T, Nagy A, Baker B, Westphal G, Halmos G and Engel JB. Human malignant melanomas express receptors for luteinizing hormone releasing hormone allowing targeted therapy with cytotoxic luteinizing hormone releasing hormone analogue. Cancer Res. 2005; 65(13):5857-5863.
24. Emons G, Sindermann H, Engel J, Schally AV and Grundker C. Luteinizing hormone-releasing hormone receptor-targeted chemotherapy using AN-152. Neuroendocrinology. 2009; 90(1):15-18.
25. Emons G, Kaufmann M, Gorchev G, Tsekova V, Grundker C, Gunthert AR, Hanker LC, Velikova M, Sindermann H, Engel J and Schally AV. Dose escalation and pharmacokinetic study of AEZS-108 (AN-152), an LHRH agonist linked to doxorubicin, in women with LHRH receptor-positive tumors. Gynecol Oncol. 2010; 119(3):457-461.
26. Liu SV, Schally AV, Hawes D, Xiong S, Fazli L, Gleave M, Cai J, Groshen S, Brands F, Engel J and Pinski J. Expression of receptors for luteinizing hormone-releasing hormone (LH-RH) in prostate cancers following therapy with LH-RH agonists. Clin Cancer Res. 2010; 16(18):4675-4680.
27. Engel J, Emons G, Pinski J and Schally AV. AEZS-108: a targeted cytotoxic analog of LHRH for the treatment of cancers positive for LHRH receptors. Expert Opin Investig Drugs. 2012; 21(6):891-899.
28. Siegel R, Naishadham D and Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012; 62(1):10-29.
29. Jacobs BL, Lee CT and Montie JE. Bladder cancer in 2010: how far have we come? CA Cancer J Clin. 2010; 60(4):244-272.
30. Calabro F and Sternberg CN. State-of-the-art management of metastatic disease at initial presentation or recurrence. World J Urol. 2006; 24(5):543-556.
31. Bahk JY, Kim MO, Park MS, Lee HY, Lee JH, Chung BC and Min SK. Gonadotropin-releasing hormone (GnRH) and GnRH receptor in bladder cancer epithelia and GnRH effect on bladder cancer cell proliferation. Urol Int. 2008; 80(4):431-438.
32. Dancik GM, Ru Y, Owens CR and Theodorescu D. A framework to select clinically relevant cancer cell lines for investigation by establishing their molecular similarity with primary human cancers. Cancer Res. 2011; 71(24):7398-7409.
33. Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med. 2002; 53:615-627.
34. Donnenberg VS and Donnenberg AD. Multiple drug resistance in cancer revisited: the cancer stem cell hypothesis. J Clin Pharmacol. 2005; 45(8):872-877.
35. Szakacs G, Paterson JK, Ludwig JA, Booth-Genthe C and Gottesman MM. Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 2006; 5(3):219-234.
36. Gyorffy B, Surowiak P and Lage H. Application of microarrays for the prediction of therapy response in breast cancer. Cancer Genomics and Proteomics 2005; 2(5):255-263.
37. Sherman-Baust CA, Becker KG, Wood Iii WH, Zhang Y and Morin PJ. Gene expression and pathway analysis of ovarian cancer cells selected for resistance to cisplatin, paclitaxel, or doxorubicin. J Ovarian Res. 2011; 4(1):21.
38. Ramachandran K, Gordian E and Singal R. 5-azacytidine reverses drug resistance in bladder cancer cells. Anticancer Res. 2011; 31(11):3757-3766.
39. Broxterman HJ, Gotink KJ and Verheul HM. Understanding the causes of multidrug resistance in cancer: a comparison of doxorubicin and sunitinib. Drug Resist Updat. 2009; 12(4-5):114-126.
40. Tan DS, Gerlinger M, Teh BT and Swanton C. Anti-cancer drug resistance: understanding the mechanisms through the use of integrative genomics and functional RNA interference. Eur J Cancer. 2010; 46(12):2166-2177.
41. Lukyanova NY, Rusetskya NV, Tregubova NA and Chekhun VF. Molecular profile and cell cycle in MCF-7 cells resistant to cisplatin and doxorubicin. Exp Oncol. 2009; 31(2):87-91.
42. Junttila TT, Laato M, Vahlberg T, Soderstrom KO, Visakorpi T, Isola J and Elenius K. Identification of patients with transitional cell carcinoma of the bladder overexpressing ErbB2, ErbB3, or specific ErbB4 isoforms: real-time reverse transcription-PCR analysis in estimation of ErbB receptor status from cancer patients. Clin Cancer Res. 2003; 9(14):5346-5357.
43. Forster JA, Paul AB, Harnden P and Knowles MA. Expression of NRG1 and its receptors in human bladder cancer. Br J Cancer. 2011; 104(7):1135-1143.
44. Kottakis F, Polytarchou C, Foltopoulou P, Sanidas I, Kampranis SC and Tsichlis PN. FGF-2 regulates cell proliferation, migration, and angiogenesis through an NDY1/KDM2B-miR-101-EZH2 pathway. Mol Cell. 2011; 43(2):285-298.
45. Icli B, Bharti A, Pentassuglia L, Peng X and Sawyer DB. ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response. Biochem Biophys Res Commun. 2012; 418(1):116-121.
46. Teng J, Wang ZY, Jarrard DF and Bjorling DE. Roles of estrogen receptor alpha and beta in modulating urothelial cell proliferation. Endocr Relat Cancer. 2008; 15(1):351-364.
47. Shen SS, Smith CL, Hsieh JT, Yu J, Kim IY, Jian W, Sonpavde G, Ayala GE, Younes M and Lerner SP. Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue. Cancer. 2006; 106(12):2610-2616.
48. Marcinkiewicz K, Scotland KB, Boorjian SA, Nilsson EM, Persson JL, Abrahamsson PA, Allegrucci C, Hughes IA, Gudas LJ and Mongan NP. The androgen receptor and stem cell pathways in prostate and bladder cancers (review). Int J Oncol. 2012; 40(1):5-12.
49. Miyamoto H, Yang Z, Chen YT, Ishiguro H, Uemura H, Kubota Y, Nagashima Y, Chang YJ, Hu YC, Tsai MY, Yeh S, Messing EM and Chang C. Promotion of bladder cancer development and progression by androgen receptor signals. J Natl Cancer Inst. 2007; 99(7):558-568.
50. Karashima T, Sweeney P, Kamat A, Huang S, Kim SJ, Bar-Eli M, McConkey DJ and Dinney CP. Nuclear factor-kappaB mediates angiogenesis and metastasis of human bladder cancer through the regulation of interleukin-8. Clin Cancer Res. 2003; 9(7):2786-2797.
51. De Luca P, Vazquez ES, Moiola CP, Zalazar F, Cotignola J, Gueron G, Gardner K and De Siervi A. BRCA1 loss induces GADD153-mediated doxorubicin resistance in prostate cancer. Mol Cancer Res. 2011; 9(8):1078-1090.
52. Rick FG, Buchholz S, Schally AV, Szalontay L, Krishan A, Datz C, Stadlmayr A, Aigner E, Perez R, Seitz S, Block NL and Hohla F. Combination of gastrin-releasing peptide antagonist with cytotoxic agents produces synergistic inhibition of growth of human experimental colon cancers. Cell Cycle. 2012; 11(13):2518-2525.
53. Rick FG, Schally AV, Block NL, Nadji M, Szepeshazi K, Zarandi M, Vidaurre I, Perez R, Halmos G and Szalontay L. Antagonists of growth hormone-releasing hormone (GHRH) reduce prostate size in experimental benign prostatic hyperplasia. Proc Natl Acad Sci U S A. 2011; 108(9):3755-3760.
54. Rick FG, Schally AV, Szalontay L, Block NL, Szepeshazi K, Nadji M, Zarandi M, Hohla F, Buchholz S and Seitz S. Antagonists of growth hormone-releasing hormone inhibit growth of androgen-independent prostate cancer through inactivation of ERK and Akt kinases. Proc Natl Acad Sci U S A. 2012; 109(5):1655-1660.
55. Rick FG, Schally AV, Block NL, Halmos G, Perez R, Fernandez JB, Vidaurre I and Szalontay L. LHRH antagonist Cetrorelix reduces prostate size and gene expression of proinflammatory cytokines and growth factors in a rat model of benign prostatic hyperplasia. Prostate. 2011; 71(7):736-747.
56. Rick FG, Szalontay L, Schally AV, Block NL, Nadji M, Szepeshazi K, Vidaurre I, Zarandi M, Kovacs M and Rekasi Z. Combining growth hormone-releasing hormone antagonist with luteinizing hormone-releasing hormone antagonist greatly augments benign prostatic hyperplasia shrinkage. J Urol. 2012; 187(4):1498-1504.