GnRH Receptor Target Therapy
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The GnRH receptor can be utilized for targeted therapies such as
- GnRH receptor-mediated chemotherapy using cytotoxic
GnRH analogs
- Hormone therapy using GnRH-I and GnRH-II analogs
- GnRH receptor-mediated gene therapy
The majority of human ovarian, endometrial and breast cancers express
GnRH receptors. Apart from reproductive organs (ovary, fallopian tube, uterus) that are normally
removed during surgical therapy of ovarian or endometrial cancer, other organs and hematopoetic
stem cells do not express GnRH receptors. In addition, a tumor specific signal transduction
exists in tumor cells, which is basically different of classical GnRH receptor signal
transduction, known to operate in pituitary gonadotrophs.
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1.) GnRH receptor targeted chemotherapy Publications:
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Westphalen S, Kotulla
G, Kaiser F, Krauß W, Werning G, Elsässer HP, Nagy A, Schulz KD, Gründker
C, Schally AV, Emons G (2000) Receptor mediated antiproliferative effects of the cytotoxic
LHRH agonist AN-152 in human ovarian and endometrial cancer cell lines. International
Journal of Oncology 17:1063-1069
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Gründker C (2000)
Cytotoxic luteinizing hormone-releasing hormone conjugates and its use in gynecological
cancer therapy. European
Journal of Endocrinology 143:569-572
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Gründker C, Völker
P, Griesinger F, Ramaswamy A, Nagy A, Schally AV, Emons G (2002) Antitumor effects of cytotoxic
LHRH analog AN-152 on human endometrial and ovarian cancers xenografted into nude mice.
American Journal
of Obstetrics and Gynecology
187:528-537
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Günthert AR, Gründker
C, Bongertz T, Nagy A, Schally AV, Emons G (2004) Induction of apoptosis by AN-152, a cytotoxic
analog of luteinizing hormone-releasing hormone (LHRH), in LHRH-R positive human breast
cancer cells is independent of multi drug resistance-1 (MDR-1) system. Breast Cancer
Research and Treatment 87:255-264
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Günthert AR,
Gründker C, Bongertz T, Schlott T, Nagy A, Schally AV, Emons G (2004) Internalisation
of cytotoxic luteinizing hormone-releasing hormone analog AN-152 induces multi drug resistance
1 (MDR-1) -independent apoptosis in human endometrial and ovarian cancer cell lines. American
Journal of Obstetrics and Gynecology 191:1164-1172
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Gründker C,
Günthert AR, Emons G (2006) Zielzellspezifische Chemotherapie über den GnRH-Rezeptor.
Frauenarzt
47(7):590-592
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Emons G, Sindermann
H, Schally AV, Gründker C (2009) LHRH receptor targeted chemotherapy using AN-152.
Neuroendocrinology 90(1):15-18
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Emons G, Kaufmann M, Gorchev
G, Tsekova V, Gründker C, Günthert AR, Hanker LC, Velikova M, Sindermann H, Engel
J, Schally AV (2010) Dose escalation and pharmacokinetic study of AEZS-108 (AN-152), an
LHRH agonist linked to doxorubicin, in women with LHRH receptor-positive tumors. Gynecologic
Oncology 119:457-461
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Föst C, Duwe
F, Hellriegel M, Schweyer S, Emons G, Gründker C (2011) Targeted chemotherapy for
triple-negative breast cancers via LHRH receptor. Oncology
Reports 25:1481-1487
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Gründker C, Ernst
J, Reutter M, Ghadimi BM, Emons G (2011) Effective targeted chemotherapy using AN-152 for
LHRH receptor-positive pancreatic cancers. Oncology Reports 26: 629-635
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Emons G, Gorchev G, Harter P,
Wimberger P, Stähle A, Hanker L, Hilpert F, Beckmann MW, Dall P,
Gründker C, Sindermann H, Sehouli J (2014) Efficacy and safety of
AEZS-108 (LHRH agonist linked
to doxorubibin) in woman with advanced or recurrent endometrial cancer
expressing LHRH receptors: a multicenter phase 2 trial (AGO GYN 5). International Journal of Gynecological Cancer 24(2):260-265
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Emons G, Gorchev G, Sehouli J,
Wimberger P, Stähle A, Hanker L, Hilpert F, Sindermann H, Gründker C, Harter P (2014) Efficacy and safety of
AEZS-108 (INN: Zoptarelin doxorubicin acetate) an LHRH agonist linked
to doxorubibin in woman with platinum refractory or resistant ovarian cancer
expressing LHRH receptors: a multicenter phase II trial of the AGO-study group (AGO GYN 5). Gynecologic Oncology 133(3):427-432
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Gründker C, Wokoun U,
Hellriegel M, Emons G (2019) Inhibition of aerobis glycolysis enhances
the anti-tumor efficacy of Zoptarelin Doxorubicin in triple-negative
breast cancer cells. The Journal of Obstetrics and Gynaecology Research
doi:10.1111/jog.13980
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2.) hormone therapy using GnRH-I and GnRH-II analogs Publications:
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Fister S, Günthert
AR, Emons G, Gründker C (2007) Gonadotropin-releasing hormone type II antagonists
induce apoptotic cell death in human endometrial and ovarian cancer cells in
vitro and in vivo.
Cancer Research 67:1750-1756
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Fister S, Günthert
AR, Aicher B, Paulini KW, Emons G, Gründker C (2009) GnRH-II antagonists induce apoptosis
in endometrial, ovarian and breast cancers via activation of stress-induced MAPKs p38 and
JNK and pro-apoptotic protein Bax. Cancer Research
69:6473-6481
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Gründker C, Föst C,
Fister S, Nolte N, Günthert AR, Emons G (2010) GnRH-II antagonist induces apoptosis
in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells in vitro and in vivo.
Breast Cancer Research 12(4):R49.
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3.) GnRH receptor-mediated gene therapyPublication:
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