Effective targeted chemotherapy using AEZS-108 (AN-152) for LHRH receptor-positive pancreatic cancers

Gründker, Carsten; Ernst, Jennifer; Reutter, Madita D.; Ghadimi, B. Michael; Emons, Günter

doi:10.3892/or.2011.1340

Cited by 14 publications

(17 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We demonstrated that treatment of GnRH receptor-positive MiaPaCa-2 and Panc-1 human pancreatic cancer cells with Zoptarelin Doxorubicin resulted in apoptosis in vitro . The antitumor effects could be also demonstrated in nude mice ( 28 ). In 2014, the first data from a multicenter phase II trial were published demonstrating that Zoptarelin Doxorubicin proved to be effective and of low toxicity in women with advanced or recurrent GnRH receptor-positive endometrial cancer ( 112 ).…”

Section: Gnrh Receptor As Target For Cancer Therapymentioning

confidence: 96%

“…Other types of tumors were found to be suitable for treatment with Zoptarelin Doxorubicin. Thirty-two percent of pancreatic cancers express GnRH receptors ( 28 ). We demonstrated that treatment of GnRH receptor-positive MiaPaCa-2 and Panc-1 human pancreatic cancer cells with Zoptarelin Doxorubicin resulted in apoptosis in vitro .…”

Section: Gnrh Receptor As Target For Cancer Therapymentioning

confidence: 99%

See 1 more Smart Citation

The Role of Gonadotropin-Releasing Hormone in Cancer Cell Proliferation and Metastasis

2017

View full text Add to dashboard Cite

In several human malignant tumors of the urogenital tract, including cancers of the endometrium, ovary, urinary bladder, and prostate, it has been possible to identify expression of gonadotropin-releasing hormone (GnRH) and its receptor as part of an autocrine system, which regulates cell proliferation. The expression of GnRH receptor has also been identified in breast cancers and non-reproductive cancers such as pancreatic cancers and glioblastoma. Various investigators have observed dose- and time-dependent growth inhibitory effects of GnRH agonists in cell lines derived from these cancers. GnRH antagonists have also shown marked growth inhibitory effects on most cancer cell lines. This indicates that in the GnRH system in cancer cells, there may not be a dichotomy between GnRH agonists and antagonists. The well-known signaling mechanisms of the GnRH receptor, which are present in pituitary gonadotrophs, are not involved in forwarding the antiproliferative effects of GnRH analogs in cancer cells. Instead, the GnRH receptor activates a phosphotyrosine phosphatase (PTP) and counteracts with the mitogenic signal transduction of growth factor receptors, which results in a reduction of cancer cell proliferation. The PTP activation, which is induced by GnRH, also inhibits G-protein-coupled estrogen receptor 1 (GPER), which is a membrane-bound receptor for estrogens. GPER plays an important role in breast cancers, which do not express the estrogen receptor α (ERα). In metastatic breast, ovarian, and endometrial cancer cells, GnRH reduces cell invasion in vitro, metastasis in vivo, and the increased expression of S100A4 and CYR61. All of these factors play important roles in epithelial–mesenchymal transition. This review will summarize the present state of knowledge about the GnRH receptor and its signaling in human cancers.

show abstract

Section: Gnrh Receptor As Target For Cancer Therapymentioning

confidence: 96%

Section: Gnrh Receptor As Target For Cancer Therapymentioning

confidence: 99%

The Role of Gonadotropin-Releasing Hormone in Cancer Cell Proliferation and Metastasis

2017

View full text Add to dashboard Cite

show abstract

“…The activation of the GnRH-R causes the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which are known as gonadotropins. Over the past decade, the GnRH-R emerged as promising drug delivery systems owing to its ectopic overexpression in a variety of human tumors such as prostate, endometrial, epithelial ovarian, bladder, breast, lymphomas, and lung cancers (Halmos et al, 2000 ; Keller et al, 2005 ; Gründker et al, 2011 ). This receptor can be addressed by agonistic peptides or small molecules in cancer therapy (Gründker and Emons, 2017 ).…”

Section: Peptide Receptors As Targets In Cancer Therapymentioning

confidence: 99%

Peptide-Drug Conjugates and Their Targets in Advanced Cancer Therapies

2020

View full text Add to dashboard Cite

Cancer became recently the leading cause of death in industrialized countries. Even though standard treatments achieve significant effects in growth inhibition and tumor elimination, they cause severe side effects as most of the applied drugs exhibit only minor selectivity for the malignant tissue. Hence, specific addressing of tumor cells without affecting healthy tissue is currently a major desire in cancer therapy. Cell surface receptors, which bind peptides are frequently overexpressed on cancer cells and can therefore be considered as promising targets for selective tumor therapy. In this review, the benefits of peptides as tumor homing agents are presented and an overview of the most commonly addressed peptide receptors is given. A special focus was set on the bombesin receptor family and the neuropeptide Y receptor family. In the second part, the specific requirements of peptide-drug conjugates (PDC) and intelligent linker structures as an essential component of PDC are outlined. Furthermore, different drug cargos are presented including classical and recent toxic agents as well as radionuclides for diagnostic and therapeutic approaches. In the last part, boron neutron capture therapy as advanced targeted cancer therapy is introduced and past and recent developments are reviewed.

show abstract

“…Many previous studies had indicated that abnormal expression of GnRH and its receptor is found in various malignant tumors, not only in a reproductive system tumors but also in non-reproductive tissues, including breast cancer, ovarian, endometrial, prostate cancer, urinary bladder cancer, pancreatic cancer, and glioblastoma, suggesting that GnRH and its receptor might be used for targeted therapy with improved anti-tumor effects (10, 11, 28). The cytotoxic GnRH agonist Zoptarelin Doxorubicin (ZEXS-106, AN-152) was more potent than doxorubicin in the inhibition of in vitro cell growth in many GnRH receptor-positive cancer cell lines (28, 29). The previous study also showed that Zoptarelin Doxorubicin is a potential therapeutic option for the treatment of triple negative breast cancer, which exhibits a higher percentage of GnRH receptor-positive tumors (30).…”

Section: Discussionmentioning

confidence: 99%

The Anti-proliferative Activity of GnRH Through Downregulation of the Akt/ERK Pathways in Pancreatic Cancer

Suo

Chang

et al. 2019

Front. Endocrinol.

View full text Add to dashboard Cite

Gonadotropin-releasing hormone (GnRH) has been demonstrated to exert anti-proliferative functions on various tumor cells in endometrial, ovarian, bladder, or prostate cancer as a part of the autocrine system. In addition, the expression levels of GnRH and its receptor had been identified in breast cancer or non-reproductive cancers, such as glioblastoma and pancreatic cancer. Previous studies have reported abnormal GnRH expression in several malignant tumors, suggesting that GnRH and its receptor might be essential for tumourigenesis. In the present study, we attempted to clarify the mechanisms underlying GnRH function in cell proliferation in pancreatic cancer. Our results indicated that GnRH expression might be essential for the malignancy of pancreatic cancer. We then found that GnRH overexpression can induce cell apoptosis through activating the Bcl-2/Bax pathway and autophagy might be involved in the GnRH-mediated apoptosis in Panc1 cells. Further investigation showed that the inhibition of GnRH may promote tumor invasion and migration through upregulation of MMP2 expression in pancreatic cancer cells. Moreover, our results indicated that GnRH can regulate the Akt/ERK1/2 pathways to promote cell proliferation by inhibiting cell apoptosis in Panc1 cells. Therefore, our finding exhibited that the regulation of GnRH expression may be essential for tumourigenesis in pancreatic cancer, and might be a potential target for the treatment of the patients with pancreatic cancer.

show abstract

Effective targeted chemotherapy using AEZS-108 (AN-152) for LHRH receptor-positive pancreatic cancers

Cited by 14 publications

References 20 publications

The Role of Gonadotropin-Releasing Hormone in Cancer Cell Proliferation and Metastasis

The Role of Gonadotropin-Releasing Hormone in Cancer Cell Proliferation and Metastasis

Peptide-Drug Conjugates and Their Targets in Advanced Cancer Therapies

The Anti-proliferative Activity of GnRH Through Downregulation of the Akt/ERK Pathways in Pancreatic Cancer

Contact Info

Product

Resources

About