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Small molecule inhibitors of the IGF-1R/IR axis for the treatment of cancer

, PhD & , PhD
Pages 605-621 | Published online: 30 Mar 2011

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Andreas Kirschner, Melanie Thiede, Thomas G. P. Grünewald, Rebeca Alba Rubio, Günther H. S. Richter, Thomas Kirchner, Dirk H. Busch, Stefan Burdach & Uwe Thiel. (2017) Pappalysin-1 T cell receptor transgenic allo-restricted T cells kill Ewing sarcoma in vitro and in vivo. OncoImmunology 6:2.
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Helena Jernberg-Wiklund & Kenneth Nilsson. (2012) Targeting the IGF-1R signaling and mechanisms for epigenetic gene silencing in human multiple myeloma. Upsala Journal of Medical Sciences 117:2, pages 166-177.
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Simona Ceccarelli, Ferdinando Romano, Antonio Angeloni & Cinzia Marchese. (2012) Potential dual role of KGF/KGFR as a target option in novel therapeutic strategies for the treatment of cancers and mucosal damages. Expert Opinion on Therapeutic Targets 16:4, pages 377-393.
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Cristina E Tognon & Poul HB Sorensen. (2012) Targeting the insulin-like growth factor 1 receptor (IGF1R) signaling pathway for cancer therapy. Expert Opinion on Therapeutic Targets 16:1, pages 33-48.
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Articles from other publishers (39)

Upendra K. Soni, Liam Jenny & Rashmi S. Hegde. (2023) IGF-1R targeting in cancer – does sub-cellular localization matter?. Journal of Experimental & Clinical Cancer Research 42:1.
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Tomoya Takeda, Masanobu Tsubaki, Shuji Genno, Kenta Tokunaga, Remi Tanaka & Shozo Nishida. (2023) HER3/Akt/mTOR pathway is a key therapeutic target for the reduction of triple‑negative breast cancer metastasis via the inhibition of CXCR4 expression. International Journal of Molecular Medicine 52:3.
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Rio S. Boothello, Nehru Viji Sankaranarayanan, Jyothi C. Sistla, Balaji Nagarajan, Chetna Sharon, John E. Chittum, Rabiya Y. Niyaz, Swarnali Roy, Aditi Nandi, Connor P. O'Hara, Rahaman Navaz Gangji, Daniel K. Afosah, Ravikumar Ongolu, Bhaumik B. Patel & Umesh R. Desai. (2022) Glycan Modulation of Insulin‐like Growth Factor‐1 Receptor. Angewandte Chemie International Edition 61:49.
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Rio S. Boothello, Nehru Viji Sankaranarayanan, Jyothi C. Sistla, Balaji Nagarajan, Chetna Sharon, John E. Chittum, Rabiya Y. Niyaz, Swarnali Roy, Aditi Nandi, Connor P. O'Hara, Rahaman Navaz Gangji, Daniel K. Afosah, Ravikumar Ongolu, Bhaumik B. Patel & Umesh R. Desai. (2022) Glycan Modulation of Insulin‐like Growth Factor‐1 Receptor. Angewandte Chemie 134:49.
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Jennifer Tsui, Shu Qi, Stephanie Perrino, Matthew Leibovitch & Pnina Brodt. (2021) Identification of a Resistance Mechanism to IGF-IR Targeting in Human Triple Negative MDA-MB-231 Breast Cancer Cells. Biomolecules 11:4, pages 527.
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Magda L Atilano, Sebastian Grönke, Teresa Niccoli, Liam Kempthorne, Oliver Hahn, Javier Morón-Oset, Oliver Hendrich, Miranda Dyson, Mirjam Lisette Adams, Alexander Hull, Marie-Therese Salcher-Konrad, Amy Monaghan, Magda Bictash, Idoia Glaria, Adrian M Isaacs & Linda Partridge. (2021) Enhanced insulin signalling ameliorates C9orf72 hexanucleotide repeat expansion toxicity in Drosophila. eLife 10.
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Christine E. LehmanAshraf A. Khalil, Mark J. AxelrodMichael I. Dougherty, Stephen S. SchoeffLinnea E. TaniguchiRolando E. MendezAbel P. DavidPatrick O. McGareyJr.,Jr.,, Matthew A. HubbardLane DonaldsonHenry F. FriersonJr.,Jr.,, Edward B. StelowStefan BekiranovJulia D. WulfkuhleEmanuel F. PetricoinDaniel G. GioeliMark J. Jameson. (2019) Antitumor effect of insulin‐like growth factor‐1 receptor inhibition in head and neck squamous cell carcinoma. The Laryngoscope 130:6, pages 1470-1478.
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Samuel Gusscott, Francesco Tamiro, Vincenzo Giambra & Andrew P. Weng. (2019) Insulin-like growth factor (IGF) signaling in T-cell acute lymphoblastic leukemia. Advances in Biological Regulation 74, pages 100652.
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Yanxin Fan, Xiuhua Bian, Pudong Qian, Jing Wen, Pengwei Yan, Yanhong Luo, Jing Wu & Qian Zhang. (2019) MiRNA‑30a‑3p inhibits metastasis and enhances radiosensitivity in esophageal carcinoma by targeting insulin‑like growth factor 1 receptor. Molecular Medicine Reports.
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Heming Li, Izhar Singh Batth, Xiujuan Qu, Ling Xu, Na Song, Ruoyu Wang & Yunpeng Liu. (2017) IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights. Molecular Cancer 16:1.
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Jingsheng Yuan, Zhijie Yin, Kaixiong Tao, Guobing Wang & Jinbo Gao. (2017) Function of insulin‑like growth factor 1 receptor in cancer resistance to chemotherapy (Review). Oncology Letters.
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Melanie I. Titze, Otmar Schaaf, Marco H. Hofmann, Michael P. Sanderson, Stephan K. Zahn, Jens Quant & Thorsten Lehr. (2017) An allometric pharmacokinetic/pharmacodynamics model for BI 893923, a novel IGF-1 receptor inhibitor. Cancer Chemotherapy and Pharmacology 79:3, pages 545-558.
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Dirk Theile, Gal Lenz, Jamil A. Momand & Susan E. Kane. 2017. Resistance to Targeted Therapies in Breast Cancer. Resistance to Targeted Therapies in Breast Cancer 35 88 .
Ciara H. O’Flanagan, Sandra O’Shea, Amy Lyons, Fionola M. Fogarty, Nuala McCabe, Richard D. Kennedy & Rosemary O’Connor. (2016) IGF-1R inhibition sensitizes breast cancer cells to ATM-related kinase (ATR) inhibitor and cisplatin. Oncotarget 7:35, pages 56826-56841.
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Melanie I. Titze, Otmar Schaaf, Marco H. Hofmann, Michael P. Sanderson, Stephan K. Zahn, Jens Quant & Thorsten Lehr. (2016) A comprehensive pharmacokinetic/pharmacodynamics analysis of the novel IGF1R/INSR inhibitor BI 893923 applying in vitro, in vivo and in silico modeling techniques. Cancer Chemotherapy and Pharmacology 77:6, pages 1303-1314.
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Chao H. Huang, Stephen K. Williamson, Prakash Neupane, Sarah A. Taylor, Ace Allen, Nora J. Smart, Adelina M. Uypeckcuat, Sarah Spencer, Jo Wick, Holly Smith, Peter J. Van Veldhuizen & Karen Kelly. (2016) Impact Study: MK-0646 (Dalotuzumab), Insulin Growth Factor 1 Receptor Antibody Combined with Pemetrexed and Cisplatin in Stage IV Metastatic Non-squamous Lung Cancer. Frontiers in Oncology 5.
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Michael P. Sanderson, Joshua Apgar, Pilar Garin-Chesa, Marco H. Hofmann, Dirk Kessler, Jens Quant, Alexander Savchenko, Otmar Schaaf, Matthias Treu, Heather Tye, Stephan K. Zahn, Andreas Zoephel, Eric Haaksma, Günther R. Adolf & Norbert Kraut. (2015) BI 885578, a Novel IGF1R/INSR Tyrosine Kinase Inhibitor with Pharmacokinetic Properties That Dissociate Antitumor Efficacy and Perturbation of Glucose Homeostasis. Molecular Cancer Therapeutics 14:12, pages 2762-2772.
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Elena Gershtein & Nikolay Kushlinskii. (2015) Clinical prospects of IGF-signaling system components study in ovarian cancer patients. Drug Metabolism and Personalized Therapy 30:2, pages 75-85.
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Heather Tye, Ulrich Guertler, Marco H. Hofmann, Moriz Mayer, Sandeep Pal, Georg Rast, Michael P. Sanderson, Otmar Schaaf, Matthias Treu & Stephan K. Zahn. (2015) Discovery of novel amino-pyrimidine inhibitors of the insulin-like growth factor 1 (IGF1R) and insulin receptor (INSR) kinases; parallel optimization of cell potency and hERG inhibition. MedChemComm 6:7, pages 1244-1251.
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Lihua Kang, Jingnan Sun, Xue Wen, Jiuwei Cui, Guanjun Wang, Andrew R. Hoffman, Ji-Fan Hu & Wei Li. (2015) Aberrant allele-switch imprinting of a novel IGF1R intragenic antisense non-coding RNA in breast cancers. European Journal of Cancer 51:2, pages 260-270.
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Thuy Vu, Mark X. Sliwkowski & Francois X. Claret. (2014) Personalized drug combinations to overcome trastuzumab resistance in HER2-positive breast cancer. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1846:2, pages 353-365.
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Jingnan Sun, Wei Li, Yunpeng Sun, Dehai Yu, Xue Wen, Hong Wang, Jiuwei Cui, Guanjun Wang, Andrew R. Hoffman & Ji-Fan Hu. (2014) A novel antisense long noncoding RNA within the IGF1R gene locus is imprinted in hematopoietic malignancies. Nucleic Acids Research 42:15, pages 9588-9601.
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Leonard Girnita, Claire Worrall, Shin-Ichiro Takahashi, Stefan Seregard & Ada Girnita. (2013) Something old, something new and something borrowed: emerging paradigm of insulin-like growth factor type 1 receptor (IGF-1R) signaling regulation. Cellular and Molecular Life Sciences 71:13, pages 2403-2427.
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Fatma Sfaxi, Nathalie Scamuffa, Claude Lalou, Jia Ma, Peter Metrakos, Géraldine Siegfried, Hermann Ragg, Andreas Bikfalvi, Fabien Calvo & Abdel-Majid Khatib. (2014) Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases. Oncotarget 5:12, pages 4195-4210.
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Annika Nordstrand, Marie Lundholm, Andreas Larsson, Ulf H. Lerner, Anders Widmark & Pernilla Wikström. (2013) Inhibition of the Insulin-Like Growth Factor-1 Receptor Enhances Effects of Simvastatin on Prostate Cancer Cells in Co-Culture with Bone. Cancer Microenvironment 6:3, pages 231-240.
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James P. DeanCynthia C. SprengerJunxiang WanKathleen HaugkWilliam J. EllisDaniel W. LinJohn M. Corman, Bruce L. DalkinElahe MostaghelPeter S. NelsonPinchas CohenBruce MontgomeryStephen R. Plymate. (2013) Response of the Insulin-Like Growth Factor (IGF) System to IGF-IR Inhibition and Androgen Deprivation in a Neoadjuvant Prostate Cancer Trial: Effects of Obesity and Androgen Deprivation. The Journal of Clinical Endocrinology & Metabolism 98:5, pages E820-E828.
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Rosalyne L. Westley & Felicity E. B. May. (2013) A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors. International Journal of Endocrinology 2013, pages 1-37.
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Valentina EvdokimovaCristina E. TognonTania BenatarWenyi YangKonstantin KrutikovMichael PollakPoul H. B. SorensenArun Seth. (2012) IGFBP7 Binds to the IGF-1 Receptor and Blocks Its Activation by Insulin-Like Growth Factors. Science Signaling 5:255.
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Ramdev Konijeti, Satomi Koyama, Ashley Gray, R. James Barnard, Jonathan W. Said, Brandon Castor, David Elashoff, Junxiang Wan, Pedro J. Beltran, Frank J. Calzone, Pinchas Cohen, Colette Galet & William J. Aronson. (2012) Effect of a Low-Fat Diet Combined with IGF-1 Receptor Blockade on 22Rv1 Prostate Cancer Xenografts. Molecular Cancer Therapeutics 11:7, pages 1539-1546.
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Benjamin W. Turney, Martin Kerr, Meenali M. Chitnis, Kunal Lodhia, Yong Wang, Johann Riedemann, Mark Rochester, Andrew S. Protheroe, Simon F. Brewster & Valentine M. Macaulay. (2012) Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks. Radiotherapy and Oncology 103:3, pages 402-409.
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Fernanda I. Arnaldez & Lee J. Helman. (2012) Targeting the Insulin Growth Factor Receptor 1. Hematology/Oncology Clinics of North America 26:3, pages 527-542.
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Li-Meng Wang, Kun-Peng Xie, Hong-Nan Huo, Fei Shang, Wei Zou & Ming-Jie Xie. (2012) Luteolin Inhibits Proliferation Induced by IGF-1 Pathway Dependent ERα in Human Breast Cancer MCF-7 Cells. Asian Pacific Journal of Cancer Prevention 13:4, pages 1431-1437.
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XIAOYING FENG, EIMAN ALEEM, YINGBO LIN, MAGNUS AXELSON, OLLE LARSSON & THOMAS STRÖMBERG. (2012) Multiple antitumor effects of picropodophyllin in colon carcinoma cell lines: Clinical implications. International Journal of Oncology 40:4, pages 1251-1258.
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Ryan P Roop & Cynthia X Ma. (2012) Endocrine resistance in breast cancer: molecular pathways and rational development of targeted therapies. Future Oncology 8:3, pages 273-292.
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Mark J. Jameson, Andrew D. Beckler, Linnea E. Taniguchi, Amir Allak, Lisa B. VanWagner, Nora G. Lee, William C. Thomsen, Matthew A. Hubbard & Christopher Y. Thomas. (2011) Activation of the Insulin-like Growth Factor-1 Receptor Induces Resistance to Epidermal Growth Factor Receptor Antagonism in Head and Neck Squamous Carcinoma Cells. Molecular Cancer Therapeutics 10:11, pages 2124-2134.
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Joseph A. Ludwig, Salah-Eddine Lamhamedi-Cherradi, Ho-Young Lee, Aung Naing & Robert Benjamin. (2011) Dual Targeting of the Insulin-Like Growth Factor and Collateral Pathways in Cancer: Combating Drug Resistance. Cancers 3:3, pages 3029-3054.
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