Abstract
Prostate cancer is the most common malignancy in men in Western countries. Until the last decade, the main available therapeutic options were based on hormonal therapy. For castration-refractory prostate carcinoma, from 2004, the combination of chemotherapy with docetaxel and prednisone has shown to improve survival in this subset of patients. Many agents have been tested either alone or in combination with this standard therapy, trying to find synergistic effects between drugs, and to target specific pathways that influence tumor growth, invasiveness, angiogenesis, and the development of distant metastasis. Endothelin antagonists have been recently studied, as they can get involved in many of these oncogenic pathways, and results are encouraging; nevertheless, the right setting to use them, whether to use them in monotherapy or in combination with other agents, and if they really improve the survival of our patients, are questions that remain to be addressed. In this review, we summarize the role of endothelins in tumoral biology and specifically in prostate carcinoma natural history, and the results obtained in the clinical trials involving this new therapeutic group.
Similar content being viewed by others
References
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.
Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502–12.
Berthold RD, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX327 study. J Clin Oncol. 2008;26:242–5.
Carducci MA, Jimeno A. Targeting bone metastasis in prostate cancer with endothelin receptor antagonists. Clin Cancer Res. 2006;12(20 Suppl):6296s–300s.
Bagnato A, Natali PG. Endothelin receptors as novel targets in tumor therapy. J Transl Med. 2004;2:16.
Obara K, Koide M, Ishikawa T, Tanabe Y, Nakayama K. Protein kinase C δ but not PKC epsilon activity is involved in contractile potentiation by endothelin-1 in the porcine coronary artery. J Cardiovasc Pharmacol. 2000;36:S120–1.
Battistini B, Chailler P, D’Orleans-Juste P, Briere N, Sirois P. Growth regulatory properties of endothelins. Peptides. 1993;14:385–99.
Nelson JB, Bagnato A, Battistini B, Nisen P. The endothelin axis: emerging role in cancer. Nat Rev Cancer. 2003;3:110–6.
Daub H, Weiss FU, Wallasch C, Ullrich A. Role of transactivation of the EGF receptor in signaling by G-protein-coupled receptors. Nature. 1996;379:557–60.
Lee JG, Zheng R, McCafferty-Cepero JM, Burnstein KL, Nanus DM, Shen R. Endothelin-1 enhances the expression of the androgen receptor via activation of the c-myc pathway in prostate cancer cells. Mol Carcinog. 2009;48(2):141–9.
Spinella F, Garrafa E, Di Castro V, Rosano L, Nicotra MR, Caruso A, et al. Endothelin-1 stimulates lymphatic endothelial cells and lymphatic vessels to grow and invade. Cancer Res. 2009;69(6):2669–76.
Grimshaw MJ. Endothelins and hypoxia-inducible factor in cancer. Endocr Relat Cancer. 2007;14(2):233–44.
Guise TA, Mohammad KS, Clines G, Stebbins EG, Wong DH, Higgins LS, et al. Basic mechanisms responsible for osteolytic and osteoblastic bone metastases. Clin Cancer Res. 2006;12:6213s–6s.
Pomonis JD, Rogers SD, Peters CM, Ghilardi JR, Mantyh PW. Expression and localization of endothelin receptors: implications for the involvement of peripheral glia in nociception. J Neurosci. 2001;21:999–1006.
Davar G. Endothelin-1 and metastatic cancer pain. Pain Med. 2001;2:24–7.
Yuyama H, Koakutsu A, Fuiyasu N, et al. Effects of selective endothelin ET(A) receptor antagonists on endothelin-1-induced potentiation of cancer pain. Eur J Pharmacol. 2004;492:177–82.
Jarvis MF, Wessale JL, Zhu CZ, et al. ABT-627, an endothelin ET(A) receptor-selective antagonist, attenuates tactile allodynia in a diabetic rat model of neuropathic pain. Eur J Pharmacol. 2000;388:29–35.
Bagnato A, Spinella F, Rosano L. Emerging role of the endothelin axis in ovarian tumor progression. Endocr Relat Cancer. 2005;12:761–72.
Felx M, Guyot MC, Isler M, Turcotte RE, Doyon J, Khatib AM, et al. Endothelin-1 (ET-1) promotes MMP-2 and MMP-9 induction involving the transcription factor NF-kappaB in human osteosarcoma. Clin Sci (Lond). 2006;110(6):645–54.
Bagnato A, Rosano L. The endothelin axis in cancer. Int J Biochem Cell Biol. 2008;40:1443–51.
Vergara D, Merlot B, Lucot JP, Collinet P, Vinatier D, Fournier I, et al. Epithelial–mesenchymal transition in ovarian cancer. Cancer Lett. 2010;291(1):59–66.
Nelson JB, Hedican SP, George DJ, et al. Identification of endothelin-1 in the pathophysiology of metastatic adenocarcinoma of the prostate. Nat Med. 1995;1:944–9.
Herrmann E, Bogemann M, Bierer S, et al. The endothelin axis in urologic tumor: mechanisms of tumor biology and therapeutic implications. Exp Rev Anticancer Ther. 2006;6:73–81.
Nelson JB, Chan-Tack K, Hedican SP, et al. Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate cancer. Cancer Res. 1996;56:663–8.
Gohji K, Kitazawa S, Tamada H, et al. Expression of endothelin receptor A associated with prostate cancer progression. J Urol. 2001;165:1033–6.
Godara G, Cannon GW, Cannon Jr GM, et al. Role of endothelin axis in progression to aggressive phenotype of prostate adenocarcinoma. Prostate. 2005;65:27–34.
Montironi R, Mazzucchelli R, Barbisan F, Stramazotti D, Santinelli A, Lopez-Beltran A, et al. Immunohistochemical expression of endothelin-1 and endothelin-A and endothelin-B receptors in high-grade prostatic intraepithelial neoplasia and prostate cancer. Eur Urol. 2007;52:1682–90.
Granchi S, Brocchi S, Bonaccorsi L, et al. Endothelin-1 production by prostate cancer cell lines is up-regulated by factors involved in cancer progression and down-regulated by androgens. Prostate. 2001;49:267–77.
Wang Y, Chen J, Li Q, et al. Identifying novel prostate cancer associated pathways based on integrative microarray data analysis. Comput Biol Chem. 2011;35(3):151–8.
Le Brun G, Aubin P, Soliman H, et al. Upregulation of endothelin 1 and its precursor by IL-1 beta, TNF-alpha, and TGF-beta in the PC3 human prostate cancer cell line. Cytokine. 1999;11(2):157–62.
Wort SJ, Ito M, Chou P, et al. Synergistic induction of endothelin-1 by tumor necrosis factor alpha and interferon gamma is due to enhanced NF-kB binding and histone acetylation at specific kB sites. J Biol Chem. 2009;284(36):24297–305.
Patrikidou A, Vlachostergios PJ, Voutsadakis IA, et al. Inverse baseline expression pattern of the NEP/neuropeptides and NFkB/proteasome pathways in androgen-dependent and androgen-independent prostate cancer cells. Cancer Cell Int. 2011;11(1):13.
Carducci MA, Padley RJ, Breul J, Vogelzang NJ, Zonnenberg BA, Daliani DD. Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: a randomized, phase II placebo-controlled trial. J Clin Oncol. 2003;21(4):679–89.
Michaelson MD, Kaufman DS, Kantoff P, Oh WK, Smith MR. Randomized phase II study of atrasentan alone or in combination with zoledronic acid in men with metastatic prostate cancer. Cancer. 2006;107:530–5.
Carducci MA, Saad F, Abrahamsson PA, Dearnaley DP, Schulman CC, North SA. A phase III randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Cancer. 2007;110(9):1959–66.
Nelson JB, Lowe W, Chin JL, Saad F, Schulman CC, Sleep DJ, et al. Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer. Cancer. 2008;113(9):2478–87.
Armstrong AJ, Creel P, Turnbull J, Moore C, Jaffe TA, Haley S, et al. A phase I-II study of docetaxel and atrasentan in men with castration-resistant metastatic prostate cancer. Clin Cancer Res. 2008;14(19):6270–6.
James ND, Caty A, Payne H, Borre M, Zonnenber BA, Beuzeboc P, et al. Final safety and efficacy analysis of the specific endothelin A receptor antagonist zibotentan in patients with metastatic castration-resistant prostate cancer and bone metastases who were pain-free or mildly symptomatic for pain: a double-blind, placebo controlled, randomized phase II trial. BJU Int. 2010;106(7):966–73.
Nelson JB, Fizazi K, Miller K, Higano CS, Moul JW, Morris T et al. Phase III study of the efficacy and safety of zibotentan (ZD4054) in patients with bone metastatic castration-resistant prostate cancer. J Clin Oncol 2011;29(suppl 7; abstr 117).
Grande M, Carlstrom K, Stege R, Pousette A, Faxen M. Estrogens affect endothelin-1 mRNA expression in LNCaP human prostate carcinoma cells. Eur Urol. 2002;41(5):568–72.
Granchi S, Brocchi S, Bonaccorsi L, et al. Endothelin-1 production by prostate cancer cell lines is up-regulated by factors involved in cancer progression and down-regulated by androgens. Prostate. 2001;49(4):267–77.
Strijbos MH, Gratama JW, Schmitz PI, et al. Circulating endothelial cells, circulating tumor cells, tissue factor, endothelin-1 and overall survival in prostate cancer patients treated with docetaxel. Eur J Cancer. 2010;46(11):2027–35.
Conflicts of interest
None
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pinto, Á., Merino, M., Zamora, P. et al. Targeting the endothelin axis in prostate carcinoma. Tumor Biol. 33, 421–426 (2012). https://doi.org/10.1007/s13277-011-0299-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-011-0299-6