ACS Publications. Most Trusted. Most Cited. Most Read
Targeted Therapy of Breast and Gynecological Cancers with Cytotoxic Analogues of Peptide Hormones

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:Mol. Pharmaceutics 2007, 4, 5, 652-658
    Articles

    Targeted Therapy of Breast and Gynecological Cancers with Cytotoxic Analogues of Peptide Hormones
    Click to copy article linkArticle link copied!

    View Author Information
    Universitätsfrauenklinik Würzburg, Josef-Schneider-Strasse 4, 97080 Würzburg, Germany, and Miller School of Medicine, University of Miami, Department of Veterans Affairs, VA Medical Center, Research Service 151, 1201 NW 16th Street, Miami, Florida 33125
    * To whom reprint requests should be addressed. Mailing address: Universitätsfrauenklinik Würzburg, Josef-Schneider-Str. 4, 97080 Würzburg, Germany. E-mail: [email protected]
    †Universitätsfrauenklinik Würzburg.
    ‡University of Miami.
    Other Access Options

    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2007, 4, 5, 652–658
    Click to copy citationCitation copied!
    https://doi.org/10.1021/mp0700514
    Published August 18, 2007
    Copyright © 2007 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    Gynecological cancers such as breast, ovarian, and endometrial carcinoma express receptors for luteinizing hormone-releasing hormone (LHRH), bombesin/gastrin-releasing peptide (BN/GRP), and somatostatin (SST). These tumors are therefore suitable candidates for targeted therapy with cytotoxic hybrid molecules consisting of a cytotoxic radical and a peptide hormone analogue as a carrier. These compounds have been shown to be more active and less toxic in vivo than nontargeted chemotherapy in models of various human cancers which express the respective receptors. The current review summarizes experimental and clinical findings with cytotoxic peptide hormone analogues of LHRH (AN-152 [AEZS 108], AN-207), BN/GRP (AN-215), and SST (AN-238) in breast, ovarian, and endometrial cancers.

    Copyright © 2007 American Chemical Society

    Subjects

    what are subjects

    Keywords

    what are keywords

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Cited By

    Click to copy section linkSection link copied!
    Citation Statements
    Explore this article's citation statements on scite.ai
    powered by  Scite

    This article is cited by 52 publications.

    1. Dylan Chapeau, Savanne Beekman, Amber Piet, Le Li, Corrina de Ridder, Debra Stuurman, Yann Seimbille. eSOMA-DM1, a Maytansinoid-Based Theranostic Small-Molecule Drug Conjugate for Neuroendocrine Tumors. Bioconjugate Chemistry 2024, 35 (11) , 1823-1834. https://doi.org/10.1021/acs.bioconjchem.4c00413
    2. Kakali De, S. K. Eashayan Tanbir, Samarendu Sinha, Soma Mukhopadhyay. Lipid-Based Nanocarrier by Targeting with LHRH Peptide: A Promising Approach for Prostate Cancer Radio-Imaging and Therapy. Molecular Pharmaceutics 2024, 21 (8) , 4128-4146. https://doi.org/10.1021/acs.molpharmaceut.4c00528
    3. Dennis J. Worm, Paul Hoppenz, Sylvia Els-Heindl, Martin Kellert, Robert Kuhnert, Stefan Saretz, Johannes Köbberling, Bernd Riedl, Evamarie Hey-Hawkins, Annette G. Beck-Sickinger. Selective Neuropeptide Y Conjugates with Maximized Carborane Loading as Promising Boron Delivery Agents for Boron Neutron Capture Therapy. Journal of Medicinal Chemistry 2020, 63 (5) , 2358-2371. https://doi.org/10.1021/acs.jmedchem.9b01136
    4. Prajakta Tambe, Pramod Kumar, Yogesh A Karpe, Kishore M Paknikar, and Virendra Gajbhiye . Triptorelin Tethered Multifunctional PAMAM-Histidine-PEG Nanoconstructs Enable Specific Targeting and Efficient Gene Silencing in LHRH Overexpressing Cancer Cells. ACS Applied Materials & Interfaces 2017, 9 (41) , 35562-35573. https://doi.org/10.1021/acsami.7b11024
    5. Nitinkumar D. Jabre, Nadiya Korostelova, and Jeremy J. Kodanko . A Highly Divergent Approach for Synthesis of Metal-Binding Peptide Libraries. The Journal of Organic Chemistry 2011, 76 (7) , 2273-2276. https://doi.org/10.1021/jo102371q
    6. Junlin Zhang, Wu Jin, Xueqing Wang, Jiancheng Wang, Xuan Zhang and Qiang Zhang. A Novel Octreotide Modified Lipid Vesicle Improved the Anticancer Efficacy of Doxorubicin in Somatostatin Receptor 2 Positive Tumor Models. Molecular Pharmaceutics 2010, 7 (4) , 1159-1168. https://doi.org/10.1021/mp1000235
    7. Christina Resta, Athanasios Moustogiannis, Eirini Chatzinikita, Dimitris Malligiannis Ntalianis, Konstantinos Malligiannis Ntalianis, Anastasios Philippou, Michael Koutsilieris, Nikolaos Vlahos. Gonadotropin-Releasing Hormone (GnRH)/GnRH Receptors and Their Role in the Treatment of Endometriosis. Cureus 2023, 220 https://doi.org/10.7759/cureus.38136
    8. Alla Pryyma, Kaveh Matinkhoo, Yong Jia Bu, Helen Merkens, Zhengxing Zhang, Francois Bénard, David M. Perrin. Synthesis and preliminary evaluation of octreotate conjugates of bioactive synthetic amatoxins for targeting somatostatin receptor (sstr2) expressing cells. RSC Chemical Biology 2022, 3 (1) , 69-78. https://doi.org/10.1039/D1CB00036E
    9. Anas Ahmad, Rajan Swami, Teenu Sharma, Atul Jain. Nanotechnology in the Management of Hormonal Cancer. 2022, 13-48. https://doi.org/10.1007/978-981-19-5558-7_2
    10. Tarun Kumar Patel, Nilanjan Adhikari, Sk. Abdul Amin, Swati Biswas, Tarun Jha, Balaram Ghosh. Small molecule drug conjugates (SMDCs): an emerging strategy for anticancer drug design and discovery. New Journal of Chemistry 2021, 45 (12) , 5291-5321. https://doi.org/10.1039/D0NJ04134C
    11. Carsten Gründker, Günter Emons. Role of Gonadotropin-Releasing Hormone (GnRH) in Ovarian Cancer. Cells 2021, 10 (2) , 437. https://doi.org/10.3390/cells10020437
    12. Hsien-Ming Wu, Hsun-Ming Chang, Peter C.K. Leung. Gonadotropin-releasing hormone analogs: Mechanisms of action and clinical applications in female reproduction. Frontiers in Neuroendocrinology 2021, 60 , 100876. https://doi.org/10.1016/j.yfrne.2020.100876
    13. J. D. Obayemi, A. A. Salifu, S. C. Eluu, V. O. Uzonwanne, S. M. Jusu, C. C. Nwazojie, C. E. Onyekanne, O. Ojelabi, L. Payne, C. M. Moore, J. A. King, W. O. Soboyejo. LHRH-Conjugated Drugs as Targeted Therapeutic Agents for the Specific Targeting and Localized Treatment of Triple Negative Breast Cancer. Scientific Reports 2020, 10 (1) https://doi.org/10.1038/s41598-020-64979-1
    14. Haralambos Tzoupis, Agathi Nteli, Maria-Eleni Androutsou, Theodore Tselios. Gonadotropin-Releasing Hormone and GnRH Receptor: Structure, Function and Drug Development. Current Medicinal Chemistry 2020, 27 (36) , 6136-6158. https://doi.org/10.2174/0929867326666190712165444
    15. Neha Mehrotra, Surender Kharbanda, Harpal Singh. Peptide-Based Combination Nanoformulations for Cancer Therapy. Nanomedicine 2020, 15 (22) , 2201-2217. https://doi.org/10.2217/nnm-2020-0220
    16. Linna Suo, Xiaocen Chang, Na Xu, Hongmei Ji. The Anti-proliferative Activity of GnRH Through Downregulation of the Akt/ERK Pathways in Pancreatic Cancer. Frontiers in Endocrinology 2019, 10 https://doi.org/10.3389/fendo.2019.00370
    17. Shaolin Ma, Sunila Pradeep, Alejandro Villar-Prados, Yunfei Wen, Emine Bayraktar, Lingegowda S. Mangala, Mark Seungwook Kim, Sherry Y. Wu, Wei Hu, Cristian Rodriguez-Aguayo, Carola Leuschner, Xiaoyan Liang, Prahlad T. Ram, Katharina Schlacher, Robert L. Coleman, Anil K. Sood. GnRH-R–Targeted Lytic Peptide Sensitizes BRCA Wild-type Ovarian Cancer to PARP Inhibition. Molecular Cancer Therapeutics 2019, 18 (5) , 969-979. https://doi.org/10.1158/1535-7163.MCT-18-0770
    18. Rongjun He, Brian Finan, John P. Mayer, Richard D. DiMarchi. Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety. Molecules 2019, 24 (10) , 1855. https://doi.org/10.3390/molecules24101855
    19. Gábor Oláh, Nikoletta Dobos, György Vámosi, Zsuzsanna Szabó, Éva Sipos, Klára Fodor, Kristóf Harda, Andrew V. Schally, Gábor Halmos. Experimental therapy of doxorubicin resistant human uveal melanoma with targeted cytotoxic luteinizing hormone-releasing hormone analog (AN-152). European Journal of Pharmaceutical Sciences 2018, 123 , 371-376. https://doi.org/10.1016/j.ejps.2018.08.002
    20. Patrizia Limonta, Marina Montagnani Marelli, Roberta Moretti, Monica Marzagalli, Fabrizio Fontana, Roberto Maggi. GnRH in the Human Female Reproductive Axis. 2018, 27-66. https://doi.org/10.1016/bs.vh.2018.01.003
    21. Carsten Gründker, Günter Emons. The Role of Gonadotropin-Releasing Hormone in Cancer Cell Proliferation and Metastasis. Frontiers in Endocrinology 2017, 8 https://doi.org/10.3389/fendo.2017.00187
    22. Samuele Cazzamalli, Alberto Dal Corso, Dario Neri. Linker stability influences the anti-tumor activity of acetazolamide-drug conjugates for the therapy of renal cell carcinoma. Journal of Controlled Release 2017, 246 , 39-45. https://doi.org/10.1016/j.jconrel.2016.11.023
    23. Yosi Gilad, Michael Firer, Gary Gellerman. Recent Innovations in Peptide Based Targeted Drug Delivery to Cancer Cells. Biomedicines 2016, 4 (2) , 11. https://doi.org/10.3390/biomedicines4020011
    24. Roberto Maggi, Anna Maria Cariboni, Marina Montagnani Marelli, Roberta Manuela Moretti, Valentina Andrè, Monica Marzagalli, Patrizia Limonta. GnRH and GnRH receptors in the pathophysiology of the human female reproductive system. Human Reproduction Update 2016, 22 (3) , 358-381. https://doi.org/10.1093/humupd/dmv059
    25. Shuang He, Zhou Zhou, Lian Li, Qingqing Yang, Yang Yang, Shan Guan, Jian Zhang, Xi Zhu, Yun Jin, Yuan Huang. Comparison of active and passive targeting of doxorubicin for somatostatin receptor 2 positive tumor models by octreotide-modified HPMA copolymer-doxorubicin conjugates. Drug Delivery 2016, 23 (1) , 285-296. https://doi.org/10.3109/10717544.2014.911991
    26. Boris Redko, Elena Ragozin, Bazylevich Andreii, Tuchinsky Helena, Albeck Amnon, Shekhter Zahavi Talia, Oron‐Herman Mor, Kostenich Genady, Gellerman Gary. Synthesis, drug release, and biological evaluation of new anticancer drug–bioconjugates containing somatostatin backbone cyclic analog as a targeting moiety. Peptide Science 2015, 104 (6) , 743-752. https://doi.org/10.1002/bip.22694
    27. C. W. Kwok, O. Treeck, S. Buchholz, S. Seitz, O. Ortmann, J. B. Engel. Receptors for luteinizing hormone-releasing hormone (GnRH) as therapeutic targets in triple negative breast cancers (TNBC). Targeted Oncology 2015, 10 (3) , 365-373. https://doi.org/10.1007/s11523-014-0340-y
    28. David Böhme, Annette G. Beck‐Sickinger. Controlling Toxicity of Peptide–Drug Conjugates by Different Chemical Linker Structures. ChemMedChem 2015, 10 (5) , 804-814. https://doi.org/10.1002/cmdc.201402514
    29. Ildikó Szabó, Szilvia Bősze, Erika Orbán, Éva Sipos, Gábor Halmos, Magdolna Kovács, Gábor Mező. Comparative in vitro biological evaluation of daunorubicin containing GnRH‐I and GnRH‐II conjugates developed for tumor targeting. Journal of Peptide Science 2015, 21 (5) , 426-435. https://doi.org/10.1002/psc.2775
    30. Stephan Seitz, Stefan Buchholz, Andrew Victor Schally, Florian Weber, Monika Klinkhammer-Schalke, Elisabeth C Inwald, Roberto Perez, Ferenc G Rick, Luca Szalontay, Florian Hohla, Sabine Segerer, Chui Wai Kwok, Olaf Ortmann, Jörg Bernhard Engel. Triple negative breast cancers express receptors for LHRH and are potential therapeutic targets for cytotoxic LHRH-analogs, AEZS 108 and AEZS 125. BMC Cancer 2014, 14 (1) https://doi.org/10.1186/1471-2407-14-847
    31. Petra Popovics, Andrew V. Schally, Luca Szalontay, Norman L. Block, Ferenc G. Rick. Targeted cytotoxic analog of luteinizing hormone-releasing hormone (LHRH), AEZS-108 (AN-152), inhibits the growth of DU-145 human castration-resistant prostate cancer in vivo and in vitro through elevating p21 and ROS levels. Oncotarget 2014, 5 (12) , 4567-4578. https://doi.org/10.18632/oncotarget.2146
    32. Rosalba Mansi, Achim Fleischmann, Helmut R. Mäcke, Jean C. Reubi. Targeting GRPR in urological cancers—from basic research to clinical application. Nature Reviews Urology 2013, 10 (4) , 235-244. https://doi.org/10.1038/nrurol.2013.42
    33. Stephan Seitz, Stefan Buchholz, Andrew V. Schally, Arumugam R. Jayakumar, Florian Weber, Andrea Papadia, Ferenc G. Rick, Luca Szalontay, Andrea Treszl, Frank Köster, Olaf Ortmann, Florian Hohla. Targeting triple-negative breast cancer through the somatostatin receptor with the new cytotoxic somatostatin analogue AN-162 [AEZS-124]. Anti-Cancer Drugs 2013, 24 (2) , 150-157. https://doi.org/10.1097/CAD.0b013e32835a7e29
    34. J.B. Engel, O. Ortmann. Endokrine Therapie des Ovarialkarzinoms. Der Gynäkologe 2012, 45 (8) , 613-617. https://doi.org/10.1007/s00129-011-2927-z
    35. J. B. Engel, A. V. Schally, S. Buchholz, S. Seitz, G. Emons, O. Ortmann. Targeted chemotherapy of endometrial, ovarian and breast cancers with cytotoxic analogs of luteinizing hormone-releasing hormone (LHRH). Archives of Gynecology and Obstetrics 2012, 286 (2) , 437-442. https://doi.org/10.1007/s00404-012-2335-1
    36. RS Struthers. Gonadotropin‐Releasing Hormone Targeting for Gonadotroph Ablation: An Approach to Non‐surgical Sterilization. Reproduction in Domestic Animals 2012, 47 (s4) , 233-238. https://doi.org/10.1111/j.1439-0531.2012.02081.x
    37. Joerg Engel, Guenter Emons, Jacek Pinski, Andrew V Schally. AEZS-108: a targeted cytotoxic analog of LHRH for the treatment of cancers positive for LHRH receptors. Expert Opinion on Investigational Drugs 2012, 21 (6) , 891-899. https://doi.org/10.1517/13543784.2012.685128
    38. Pallavi Kapoor, Harinder Singh, Ankur Gautam, Kumardeep Chaudhary, Rahul Kumar, Gajendra P. S. Raghava, . TumorHoPe: A Database of Tumor Homing Peptides. PLoS ONE 2012, 7 (4) , e35187. https://doi.org/10.1371/journal.pone.0035187
    39. Pascal Schlage, Gábor Mező, Erika Orbán, Szilvia Bősze, Marilena Manea. Anthracycline-GnRH derivative bioconjugates with different linkages: Synthesis, in vitro drug release and cytostatic effect. Journal of Controlled Release 2011, 156 (2) , 170-178. https://doi.org/10.1016/j.jconrel.2011.08.005
    40. Lichun Sun, Lynsie M. Morris, Jing Luo, L. Vienna Mackey, Juliana S. Leslie, Laura G. Franko-Tobin, Joseph A. Fuselier, Keith T. LePage, David H. Coy. Application of human pancreatic carcinoid BON cells for receptor-targeted drug development. Journal of Drug Targeting 2011, 19 (8) , 666-674. https://doi.org/10.3109/1061186X.2010.531728
    41. Lichun Sun, Jing Luo, L. Vienna Mackey, Lynsie M. Morris, Laura G. Franko-Tobin, Keith T. LePage, David H. Coy. Investigation of cancer cell lines for peptide receptor-targeted drug development. Journal of Drug Targeting 2011, 19 (8) , 719-730. https://doi.org/10.3109/1061186X.2011.558089
    42. Günter Emons, Manfred Kaufmann, Grigor Gorchev, Valentina Tsekova, Carsten Gründker, Andreas R. Günthert, Lars C. Hanker, Maya Velikova, Herbert Sindermann, Jürgen Engel, Andrew V. Schally. 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 2010, 119 (3) , 457-461. https://doi.org/10.1016/j.ygyno.2010.08.003
    43. Xin Ming, Md Rowshon Alam, Michael Fisher, Yongjun Yan, Xiaoyuan Chen, Rudolph L. Juliano. Intracellular delivery of an antisense oligonucleotide via endocytosis of a G protein-coupled receptor. Nucleic Acids Research 2010, 38 (19) , 6567-6576. https://doi.org/10.1093/nar/gkq534
    44. J.B. Engel, A. Hönig, K. Diedrich, J. Dietl, F. Köster. Endokrine Therapie der Zukunft. Gynäkologische Endokrinologie 2010, 8 (1) , 47-54. https://doi.org/10.1007/s10304-009-0327-4
    45. Maria Cristina De Martino, Leo J. Hofland, Steven W.J. Lamberts. Somatostatin and Somatostatin Receptors: from Basic Concepts to Clinical Applications. 2010, 255-280. https://doi.org/10.1016/S0079-6123(10)82011-4
    46. Stephan Seitz, Andrew V. Schally, Andrea Treszl, Andrea Papadia, Ferenc Rick, Luca Szalontay, Karoly Szepeshazi, Olaf Ortmann, Gabor Halmos, Florian Hohla, Stefan Buchholz. Preclinical evaluation of properties of a new targeted cytotoxic somatostatin analog, AN-162 (AEZS-124), and its effects on tumor growth inhibition. Anti-Cancer Drugs 2009, 20 (7) , 553-558. https://doi.org/10.1097/CAD.0b013e32832d190b
    47. Thanh H Dellinger, Bradley J Monk. Systemic therapy for recurrent endometrial cancer: a review of North American trials. Expert Review of Anticancer Therapy 2009, 9 (7) , 905-916. https://doi.org/10.1586/era.09.54
    48. . Current World Literature. Current Opinion in Obstetrics & Gynecology 2009, 101-109. https://doi.org/10.1097/GCO.0b013e3283240745
    49. R.T. Jensen, J.F. Battey, E.R. Spindel, R.V. Benya. International Union of Pharmacology. LXVIII. Mammalian Bombesin Receptors: Nomenclature, Distribution, Pharmacology, Signaling, and Functions in Normal and Disease States. Pharmacological Reviews 2008, 60 (1) , 1-42. https://doi.org/10.1124/pr.107.07108
    50. Nieves Gonzalez, Terry W Moody, Hisato Igarashi, Tetsuhide Ito, Robert T Jensen. Bombesin-related peptides and their receptors: recent advances in their role in physiology and disease states. Current Opinion in Endocrinology, Diabetes & Obesity 2008, 15 (1) , 58-64. https://doi.org/10.1097/MED.0b013e3282f3709b
    51. . Current World Literature. Current Opinion in Endocrinology, Diabetes & Obesity 2008, 79-111. https://doi.org/10.1097/MED.0b013e3282f4f084
    52. Christophe Van de Wiele, Philippe Phonteyne, Patrick Pauwels, Ingeborg Goethals, Rudi Van den Broecke, Veronique Cocquyt, Rudi Andre Dierckx. Gastrin-Releasing Peptide Receptor Imaging in Human Breast Carcinoma Versus Immunohistochemistry. Journal of Nuclear Medicine 2008, 49 (2) , 260-264. https://doi.org/10.2967/jnumed.107.047167
    Download PDF
    Go to Molecular Pharmaceutics
    Get e-Alerts
    Get e-Alerts

    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2007, 4, 5, 652–658
    Click to copy citationCitation copied!
    https://doi.org/10.1021/mp0700514
    Published August 18, 2007
    Copyright © 2007 American Chemical Society
    Request reuse permissions

    Article Views

    893

    Altmetric

    -

    Citations

    52
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.