View More View Less
  • 1 Országos Onkológiai Intézet, Budapest, Ráth György u. 7–9., 1122
Full access

Absztrakt:

A metasztatikus kasztrációrezisztens prosztatadaganat kezelésében az elmúlt hat évben öt új hatóanyag került törzskönyvezésre. E szerek szekvenciális alkalmazásával ebben a továbbra is gyógyíthatatlan betegségben jelentős túlélést lehet elérni, jó életminőség mellett. Az elmúlt évtized kutatásainak köszönhetően, egyértelművé vált, hogy a betegség progressziójának középpontjában az androgénreceptor mediálta folyamatok állnak. Az androgénreceptort érintő hormonális mechanizmusok a betegség késői stádiumáig funkcióképesek maradhatnak. Ezeknek a mechanizmusoknak még pontosabb megismerése vezetett a nómenklatúra megváltoztatásához, az új endokrin terápiák bevezetéséhez. Az új terápiák során jelentkező primer, illetve szekunder rezisztencia hátterében álló androgénreceptor-mutációk identifikálása, remodellezése újabb, még hatékonyabb androgénreceptor-gátló kezelésekhez nyithat utat. A szerzők ismertetik az androgénreceptorszignál-tengely patofiziológiáját, receptoriális szinten bemutatják a már engedélyezett gyógyszereket, valamint felhívják a figyelmet a legígéretesebbnek tűnő fejlesztésekre is. Orv. Hetil., 2017, 158(2), 42–49.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1

    Huggins, C., Hodges, C.: Studies on prostatic cancer. I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res., 1941, 1, 293–297.

  • 2

    Sweeney, C., Chen, Y. H., Carducci, M., et al.: Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): An ECOG-led phase III randomized trial. 2014 ASCO Annual Meeting. J. Clin. Oncol., 2014, 32(5 Suppl.), Abstract LBA2.

  • 3

    Sweeney, C. J., Chen, Y. H., Carducci, M., et al.: Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N. Engl. J. Med., 2015, 373, 737–746.

  • 4

    Longo, D. L.: New therapies for castration-resistant prostate cancer. N. Engl. J. Med., 2010, 363(5), 479–481.

  • 5

    EAU Guidelines on Prostate Cancer. http://www.uroweb.org

  • 6

    Friedlander, T. W., Ryan, C. J.: Targeting the androgen receptor. Urol. Clin. North Am., 2012, 39(4), 453–464.

  • 7

    Sadar, M. D.: Small molecule inhibitors targeting the “achilles’ heel” of androgen receptor activity. Cancer Res., 2011, 71(4), 1208–1213.

  • 8

    Zoubeidi, A., Zardan, A., Beraldi, E., et al.: Cooperative interactions between androgen receptor (AR) and heat-shock protein 27 facilitate AR transcriptional activity. Cancer Res., 2007, 67(21), 10455–10465.

  • 9

    Knudsen, K. E., Kelly, W. K.: Outsmarting androgen receptor: creative approaches for targeting aberrant androgen signaling in advanced prostate cancer. Expert Rev. Endocrinol. Metab., 2011, 6(3), 483–493.

  • 10

    Küronya, Z., Bíró, K., Géczy, L., et al.: Treatment strategies for advanced prostate cancer. [Kezelési stratégiák előrehaladott prosztatadaganatban.] Magy. Onkol., 2015, 59(3), 229–240. [Hungarian]

  • 11

    Oh, W. K.: The evolving role of estrogen therapy in prostate cancer. Clin. Prostate Cancer, 2002, 1(2), 81–89.

  • 12

    Seidenfeld, J., Samson, D. J., Hasselblad, V., et al.: Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann. Intern. Med., 2000, 132(7), 566–577.

  • 13

    Klotz, L., Boccon-Gibod, L., Shore, N. D., et al.: The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int., 2008, 102(11), 1531–1538.

  • 14

    Taylor, C. D., Elson, P., Trump, D. L.: Importance of continued testicular suppression in hormone-refractory prostate cancer. J. Clin. Oncol., 1993, 11(11), 2167–2172.

  • 15

    Yin, L., Hu, Q.: CYP17 inhibitors – abiraterone, C17,20-lyase inhibitors and multi-targeting agents. Nat. Rev. Urol., 2014, 11(1), 32–42.

  • 16

    Trump, D. L., Havlin, K. H., Messing, E. M., et al.: High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects. J. Clin. Oncol., 1989, 7(8), 1093–1098.

  • 17

    De Bono, J. S., Logothetis, C. J., Molina, A., et al.: Abiraterone and increased survival in metastatic prostate cancer. N. Engl. J. Med., 2011, 364(21), 1995–2005.

  • 18

    Ryan, C. J., Smith, M. R., de Bono, J. S., et al.: Abiraterone in metastatic prostate cancer without previous chemotherapy. N. Engl. J. Med., 2013, 368(2), 138–148.

  • 19

    Kaku, T., Hitaka, T., Ojida, A., et al.: Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer. Bioorg. Med. Chem., 2011, 19(21), 6383–6399.

  • 20

    Fizazi, K., Jones, R., Oudard, S., et al.: Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5. J. Clin. Oncol., 2015, 33(7), 723–731.

  • 21

    Prostate Cancer Trialists’ Collaborative Group: Maximum androgen blockade in advanced prostate cancer: an overview of the randomised trials. Lancet, 2000, 355(9214), 1491–1498.

  • 22

    Gillessen, S., Omlin, A., Attard, G., et al.: Management of patients with advanced prostate cancer: recommendations of the St. Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015. Ann. Oncol., 2015, 26(4), 1589–1604.

  • 23

    Scher, H. I., Fizazi, K., Saad, F., et al.: Increased survival with enzalutamide in prostate cancer after chemotherapy. N. Engl. J. Med., 2012, 367(13), 1187–1197.

  • 24

    Loriot, Y., Miller, K., Sternberg, C. N., et al.: Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial. Lancet Oncol., 2015, 16(5), 509–521.

  • 25

    Rathkopf, D. E., Morris, M. J., Fox, J. J., et al.: Phase I study of ARN-509, a novel antiandrogen, in the treatment of castration-resistant prostate cancer. J. Clin. Oncol., 2013, 31(28), 3525–3530.

  • 26

    Moilanen, A. M., Riikonen, R., Oksala, R., et al.: Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. Sci. Rep., 2015, 5, 12007.

  • 27

    Zhang, H., Zhan, Y., Liu, X., et al.: Splicing variants of androgen receptor in prostate cancer. Am. J. Clin. Exp. Urol., 2013, 1(1), 18–24.

  • 28

    Antonarakis, E. S., Lu, C., Wang, H., et al.: AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N. Engl. J. Med., 2014, 371(11), 1028–1038.

  • 29

    Antonarakis, E. S.: Predicting treatment response in castration-resistant prostate cancer: could androgen receptor variant-7 hold the key? Expert Rev. Anticancer Ther., 2015, 15(2), 143–145.

  • 30

    Njar, V. C., Brodie, A. M.: Discovery and development of Galeterone (TOK-001 or VN/124-1) for the treatment of all stages of prostate cancer. J. Med. Chem., 2015, 58(5), 2077–2087.

  • 31

    Liu, C., Lou, W., Zhu, Y., et al.: Niclosamide inhibits androgen receptor variants expression and overcomes enzalutamide resistance in castration-resistant prostate cancer. Clin. Cancer Res., 2014, 20(12), 3198–3210.

  • 32

    Wadosky, K. M., Koochekpour, S.: Therapeutic rationales, progresses, failures, and future directions for advanced prostate cancer. Int. J. Biol. Sci., 2016, 12(4), 409–426.

  • 33

    Heath, E. I., Hillman, D. W., Vaishampayan, U., et al.: A phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer. Clin. Cancer Res., 2008, 14(23), 7940–7946.

  • 34

    Oh, W. K., Galsky, M. D., Stadler, W. M., et al.: Multicenter phase II trial of the heat shock protein 90 inhibitor, retaspimycin hydrochloride (IPI-504), in patients with castration-resistant prostate cancer. Urology, 2011, 78(3), 626–630.

  • 35

    Sonpavde, G., Matveev, V., Burke, J. M., et al.: Randomized phase II trial of docetaxel plus prednisone in combination with placebo or AT-101, an oral small molecule Bcl-2 family antagonist, as first-line therapy for metastatic castration-resistant prostate cancer. Ann. Oncol., 2012, 23(7), 1803–1808.

  • 36

    Myung, J. K., Banuelos, C. A., Fernandez, J. G., et al.: An androgen receptor N-terminal domain antagonist for treating prostate cancer. J. Clin. Investigation, 2013, 123(7), 2948–2960.

  • Impact Factor (2018): 0.564
  • Medicine (miscellaneous) SJR Quartile Score (2018): Q3
  • Scimago Journal Rank (2018): 0.193
  • SJR Hirsch-Index (2018): 18

Language: Hungarian

Founded in 1857
Publication: Weekly, one volume of 52 issues annually

Senior editors

Editor(s)-in-Chief: Papp Zoltán

Read the professional career of Papp Zoltán HERE.

 

Editorial Board

Click for the Editorial Board

Akadémiai Kiadó
Address: Prielle Kornélia u. 21-35. H-1117 Budapest, Hungary
Phone: (+36 1) 464 8235 ---- Fax: (+36 1) 464 8221
Email: orvosihetilap@akkrt.hu

The author instructions are available in PDF.
Instructions for Authors in Hungarian HERE.

Mendeley citation style is available HERE.

 

MANUSCRIPT SUBMISSION