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At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2020

01-12-2020 | Insulins | Review

Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy

Authors: Hui Hua, Qingbin Kong, Jie Yin, Jin Zhang, Yangfu Jiang

Published in: Journal of Hematology & Oncology | Issue 1/2020

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Abstract

Insulin-like growth factors (IGFs) play important roles in mammalian growth, development, aging, and diseases. Aberrant IGFs signaling may lead to malignant transformation and tumor progression, thus providing the rationale for targeting IGF axis in cancer. However, clinical trials of the type I IGF receptor (IGF-IR)-targeted agents have been largely disappointing. Accumulating evidence demonstrates that the IGF axis not only promotes tumorigenesis, but also confers resistance to standard treatments. Furthermore, there are diverse pathways leading to the resistance to IGF-IR-targeted therapy. Recent studies characterizing the complex IGFs signaling in cancer have raised hope to refine the strategies for targeting the IGF axis. This review highlights the biological activities of IGF-IR signaling in cancer and the contribution of IGF-IR to cytotoxic, endocrine, and molecular targeted therapies resistance. Moreover, we update the diverse mechanisms underlying resistance to IGF-IR-targeted agents and discuss the strategies for future development of the IGF axis-targeted agents.
Literature
1.
2.
Roddam AW, Allen NE, Appleby P, Key TJ, Ferrucci L, Carter HB, et al. Insulin-like growth factors, their binding proteins, and prostate cancer risk: analysis of individual patient data from 12 prospective studies. Ann Intern Med. 2008;149:461–71.PubMedPubMedCentralCrossRef
3.
Price AJ, Allen NE, Appleby PN, Crowe FL, Travis RC, Tipper SJ, et al. Insulin-like growth factor-I concentration and risk of prostate cancer: results from the European Prospective Investigation into Cancer and Nutrition. Cancer Epidemiol Biomark Prev. 2012;21:1531–41.CrossRef
4.
Ho GYF, Zheng SL, Cushman M, Perez-Soler R, Kim M, Xue X, et al. Associations of insulin and IGFBP-3 with lung cancer susceptibility in current smokers. J Natl Cancer Inst. 2016;108:djw012.PubMedCentralCrossRef
5.
Yoon YS, Keum N, Zhang X, Cho E, Giovannucci EL. Circulating levels of IGF-1, IGFBP-3, and IGF-1/IGFBP-3 molar ratio and colorectal adenomas: a meta-analysis. Cancer Epidemiol. 2015;39:1026–35.PubMedCrossRef
6.
Adachi Y, Nojima M, Mori M, Yamashita K, Yamano HO, Nakase H, et al. Insulin-like growth factor-1, IGF binding protein-3, and the risk of esophageal cancer in a nested case-control study. World J Gastroenterol. 2017;23:3488–95.PubMedPubMedCentralCrossRef
7.
Adachi Y, Nojima M, Mori M, Kubo T, Yamano HO, Lin Y, et al. Circulating insulin-like growth factor binding protein-3 and risk of gastrointestinal malignant tumors. J Gastroenterol Hepatol. 2019;34:2104–11.PubMedCrossRef
8.
Lin C, Travis RC, Appleby PN, Tipper S, Weiderpass E, Chang-Claude J, et al. Pre-diagnostic circulating insulin-like growth factor-I and bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2018;143:2351–8.PubMedPubMedCentralCrossRef
9.
Perez-Cornago A, Appleby PN, Tipper S, et al. Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2017;140:1111–8.PubMedCrossRef
10.
Bradbury KE, Appleby PN, Tipper SJ, Key TJ, Allen NE, Nieters A, et al. Circulating insulin-like growth factor I in relation to melanoma risk in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2019;144:957–66.PubMed
11.
Chng WJ, Gualberto A, Fonseca R. IGF-1R is overexpressed in poor-prognostic subtypes of multiple myeloma. Leuk Res. 2006;20:174–6.
12.
Sprynski AC, Hose D, Kassambara A, Vincent L, Jourdan M, Rossi JF, et al. Insulin is a potent myeloma cell growth factor through insulin/IGF-1 hybrid receptor activation. Leuk Res. 2010;24:1940–50.
13.
Vishwamitra D, George SK, Shi P, Kaseb AO, Amin HM. Type I insulin-like growth factor receptor signaling in hematological malignancies. Oncotarget. 2017;8:1814–44.PubMedCrossRef
14.
15.
Medyouf H, Gusscott S, Wang H, Tseng JC, Wai C, Nemirovsky O, et al. High-level IGF1R expression is required for leukemia-initiating cell activity in T-ALL and is supported by notch signaling. J Exp Med. 2011;208:1809–22.PubMedPubMedCentralCrossRef
16.
Lakshmikuttyamma A, Pastural E, Takahashi N, Sawada K, Sheridan DP, DeCoteau JF, et al. Bcr-Abl induces autocrine IGF-1 signaling. Oncogene. 2008;27:3831–44.PubMedCrossRef
17.
Doepfner KT, Spertini O, Arcaro A. Autocrine insulin-like growth factor-I signaling promotes growth and survival of human acute myeloid leukemia cells via the phosphoinositide 3-kinase/Akt pathway. Leukemia. 2007;21:1921–30.PubMedCrossRef
18.
Yaktapour N, Übelhart R, Schüler J, Aumann K, Dierks C, Burger M, et al. Insulin-like growth factor-1 receptor (IGF1R) as a novel target in chronic lymphocytic leukemia. Blood. 2013;122:1621–33.PubMedCrossRef
19.
Shi P, Lai R, Lin Q, Iqbal AS, Young LC, Kwak LW, et al. IGF-IR tyrosine kinase interacts with NPM-ALK oncogene to induce survival of T-cell ALK+ anaplastic large-cell lymphoma cells. Blood. 2009;114:360–70.PubMedPubMedCentralCrossRef
20.
Mitsiades CS, Mitsiades NS, McMullan CJ, Poulaki V, Shringarpure R, Akiyama M, et al. Inhibition of the insulin-like growth factor receptor-1 tyrosine kinase activity as a therapeutic strategy for multiple myeloma, other hematologic malignancies, and solid tumors. Cancer Cell. 2004;5:221–30.PubMedCrossRef
21.
Maris C, D’Haene N, Trépant AL, Le Mercier M, Sauvage S, Allard J, et al. IGF-IR: a new prognostic biomarker for human glioblastoma. Br J Cancer. 2015;113:729–37.PubMedPubMedCentralCrossRef
22.
Khatib AM, Siegfried G, Prat A, Luis J, Chrétien M, Metrakos P, et al. Inhibition of proprotein convertases is associated with loss of growth and tumorigenicity of HT-29 human colon carcinoma cells: importance of insulin-like growth factor-1 (IGF-1) receptor processing in IGF-1-mediated functions. J Biol Chem. 2001;276:30686–93.PubMedCrossRef
23.
LeRoith D, Werner H, Beitner-Johnson D, Roberts CT Jr. Molecular and cellular aspects of the insulin-like growth factor I receptor. Endocr Rev. 1995;16:143–63.PubMedCrossRef
24.
Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, Collins C, et al. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 1986;5:2503–12.PubMedPubMedCentralCrossRef
25.
Seino S, Bell GI. Alternative splicing of human insulin receptor messenger RNA. Biochem Biophys Res Commun. 1989;159:312–6.PubMedCrossRef
26.
Evdokimova V, Tognon CE, Benatar T, Yang W, Krutikov K, Pollak M, et al. IGFBP7 binds to the IGF-1 receptor and blocks its activation by insulin-like growth factors. Sci Signal. 2012;5:ra92.PubMedCrossRef
27.
Yee D. Anti-insulin-like growth factor therapy in breast cancer. J Mol Endocrinol. 2018;61:T61–8.PubMedCrossRef
28.
Taniguchi CM, Emanuelli B, Kahn CR. Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol. 2006;7:85–96.PubMedCrossRef
29.
Liu D, Rutter WJ, Wang LH. Modulating effects of the extracellular sequence of the human insulin-like growth factor I receptor on its transforming and tumorigenic potential. J Virol. 1993;67:9–18.PubMedPubMedCentralCrossRef
30.
Lee JH, Choi SI, Kim RK, Cho EW, Kim IG. Tescalcin/c-Src/IGF1Rβ-mediated STAT3 activation enhances cancer stemness and radioresistant properties through ALDH1. Sci Rep. 2018;8:10711.PubMedPubMedCentralCrossRef
31.
Tahimic CG, Long RK, Kubota T, Sun MY, Elalieh H, Fong C, et al. Regulation of ligand and shear stress-induced insulin-like growth factor 1 (IGF1) signaling by the integrin pathway. J Biol Chem. 2016;291:8140–9.PubMedPubMedCentralCrossRef
32.
Yin Y, Hua H, Li M, Liu S, Kong Q, Shao T, et al. mTORC2 promotes type I insulin-like growth factor receptor and insulin receptor activation through the tyrosine kinase activity of mTOR. Cell Res. 2016;26:46–65.PubMedCrossRef
33.
De Meyts P, Shymko RM. Timing-dependent modulation of insulin mitogenic versus metabolic signalling. Novartis Found Symp. 2000;227:46–57.PubMed
34.
Accili D, Drago J, Lee EJ, Johnson MD, Cool MH, Salvatore P, et al. Early neonatal death in mice homozygous for a null allele of the insulin receptor gene. Nat Genet. 1996;12:106–9.PubMedCrossRef
35.
Farabaugh SM, Boone DN, Lee AV. Role of IGF1R in breast cancer subtypes, stemness, and lineage differentiation. Front Endocrinol (Lausanne). 2015;6:59.CrossRef
36.
Peiró G, Adrover E, Sánchez-Tejada L, Lerma E, Planelles M, Sánchez-Payá J, et al. Increased insulin-like growth factor-1 receptor mRNA expression predicts poor survival in immunophenotypes of early breast carcinoma. Mod Pathol. 2011;24:201–8.PubMedCrossRef
37.
Law JH, Habibi G, Hu K, Masoudi H, Wang MY, Stratford AL, et al. Phosphorylated insulin-like growth factor-i/insulin receptor is present in all breastcancer subtypes and is related to poor survival. Cancer Res. 2008;68:10238–46.PubMedCrossRef
38.
Creighton CJ, Casa A, Lazard Z, Huang S, Tsimelzon A, Hilsenbeck SG, et al. Insulin-like growth factor-I activates gene transcription programs strongly associated with poor breast cancer prognosis. J Clin Oncol. 2008;26:4078–85.PubMedPubMedCentralCrossRef
39.
Yerushalmi R, Gelmon KA, Leung S, Gao D, Cheang M, Pollak M, et al. Insulin-like growth factor receptor (IGF-1R) in breast cancer subtypes. Breast Cancer Res Treat. 2012;132:131–42.PubMedCrossRef
40.
Mountzios G, Aivazi D, Kostopoulos I, Goldbogen J, Southall B. Differential expression of the insulin-like growth factor receptor among early breast cancer subtypes. PLoS One. 2014;9:e91407.PubMedPubMedCentralCrossRef
41.
Aleksic T, Verrill C, Bryant RJ, Han C, Worrall AR, Brureau L, et al. IGF-1R associates with adverse outcomes after radical radiotherapy for prostate cancer. Br J Cancer. 2017;117:1600–6.PubMedPubMedCentralCrossRef
42.
Dale OT, Aleksic T, Shah KA, Han C, Mehanna H, Rapozo DC, et al. IGF-1R expression is associated with HPV-negative status and adverse survival in head and neck squamous cell cancer. Carcinogenesis. 2015;36:648–55.PubMedCrossRef
43.
Moreno-Acosta P, Vallard A, Carrillo S, Gamboa O, Romero-Rojas A, Molano M, et al. Biomarkers of resistance to radiation therapy: a prospective study in cervical carcinoma. Radiat Oncol. 2017;12:120.PubMedPubMedCentralCrossRef
44.
45.
Giorgetti S, Ballotti R, Kowalski-Chauvel A, Tartare S, Van Obberghen E. The insulin and insulin-like growth factor-I receptor substrate IRS-1 associates with and activates phosphatidylinositol 3-kinase in vitro. J Biol Chem. 1993;268:7358–64.PubMed
46.
47.
Nitulescu GM, Van De Venter M, Nitulescu G, Nitulescu G, Ungurianu A, Juzenas P, et al. The Akt pathway in oncology therapy and beyond. Int J Oncol. 2018;53:2319–31.PubMedPubMedCentral
48.
Qin X, Li J, Sun J, Liu L, Chen D, Liu Y. Low shear stress induces ERK nuclear localization and YAP activation to control the proliferation of breast cancer cells. Biochem Biophys Res Commun. 2019;510:219–23.PubMedCrossRef
49.
Zhu H, Wang DD, Yuan T, Yan FJ, Zeng CM, Dai XY, et al. Multikinase inhibitor CT-707 targets liver cancer by interrupting the hypoxia-activated IGF-1R-YAP axis. Cancer Res. 2018;78:3995–4006.PubMedCrossRef
50.
Straßburger K, Tiebe M, Pinna F, Breuhahn K, Teleman AA. Insulin/IGF signaling drives cell proliferation in part via Yorkie/YAP. Dev Biol. 2012;367:187–96.PubMedCrossRef
51.
Ravid D, Maor S, Werner H, Liscovitch M. Caveolin-1 inhibits cell detachment-induced p53 activation and anoikis by upregulation of insulin-like growth factor-I receptors and signaling. Oncogene. 2005;24:1338–47.PubMedCrossRef
52.
Zhang W, Zong CS, Hermanto U, Lopez-Bergami P, Ronai Z, Wang LH. RACK1 recruits STAT3 specifically to insulin and insulin-like growth factor 1 receptors for activation, which is important for regulating anchorage-independent growth. Mol Cell Biol. 2006;26:413–24.PubMedPubMedCentralCrossRef
53.
Kiely PA, Sant A, O’Connor R. RACK1 is an insulin-like growth factor 1 (IGF-1) receptor-interacting protein that can regulate IGF-1-mediated Akt activation and protection from cell death. J Biol Chem. 2002;277:22581–9.PubMedCrossRef
54.
55.
Sachdev D, Zhang X, Matise I, Gaillard-Kelly M, Yee D. The type I insulin-like growth factor receptor regulates cancer metastasis independently of primary tumor growth by promoting invasion and survival. Oncogene. 2010;29:251–62.PubMedCrossRef
56.
Varkaris A, Gaur S, Parikh NU, Song JH, Dayyani F, Jin JK, et al. Ligand-independent activation of MET through IGF-1/IGF-1R signaling. Int J Cancer. 2013;133:1536–46.PubMedPubMedCentralCrossRef
57.
Jaquish DV, Yu PT, Shields DJ, French RP, Maruyama KP, Niessen S, et al. IGF1-R signals through the RON receptor to mediate pancreatic cancer cell migration. Carcinogenesis. 2011;32:1151–6.PubMedPubMedCentralCrossRef
58.
Svalina MN, Kikuchi K, Abraham J, Lal S, Davare MA, Settelmeyer TP, et al. IGF1R as a key target in high risk, metastatic medulloblastoma. Sci Rep. 2016;6:27012.PubMedPubMedCentralCrossRef
59.
Vella V, Malaguarnera R, Nicolosi ML, Morrione A, Belfiore A. Insulin/IGF signaling and discoidin domain receptors: an emerging functional connection. Biochim Biophys Acta, Mol Cell Res. 2019;1866:118522.CrossRef
60.
Azizi R, Salemi Z, Fallahian F, Aghaei M. Inhibition of didscoidin domain receptor 1 reduces epithelial-mesenchymal transition and induce cell-cycle arrest and apoptosis in prostate cancer cell lines. J Cell Physiol. 2019;234:19539–52.PubMedCrossRef
61.
Cheng J, He S, Wang M, Zhou L, Zhang Z, Feng X, et al. The caspase-3/PKCδ/Akt/VEGF-A signaling pathway mediates tumor repopulation during radiotherapy. Clin Cancer Res. 2019;25:3732–43.PubMedCrossRef
62.
Datta K, Nambudripad R, Pal S, Zhou M, Cohen HT, Mukhopadhyay D. Inhibition of insulin-like growth factor-I-mediated cell signaling by the von Hippel-Lindau gene product in renal cancer. J Biol Chem. 2000;275:20700–6.PubMedCrossRef
63.
Lyons A, Coleman M, Riis S, Favre C, O’Flanagan CH, Zhdanov AV, et al. Insulin-like growth factor 1 signaling is essential for mitochondrial biogenesis and mitophagy in cancer cells. J Biol Chem. 2017;292:16983–98.PubMedPubMedCentralCrossRef
64.
Yang Y, Yee D. IGF-I regulates redox status in breast cancer cells by activating the amino acid transport molecule xC-. Cancer Res 2014;74:2295-305.
65.
Logan S, Pharaoh GA, Marlin MC, Masser DR, Matsuzaki S, Wronowski B, et al. Insulin-like growth factor receptor signaling regulates working memory, mitochondrial metabolism, and amyloid-β uptake in astrocytes. Mol Metab. 2018;9:141–55.PubMedPubMedCentralCrossRef
66.
Li H, Batth IS, Qu X, Xu L, Song N, Wang R, et al. IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights. Mol Cancer. 2017;16:6.PubMedPubMedCentralCrossRef
67.
Taliaferro-Smith L, Oberlick E, Liu T, McGlothen T, Alcaide T, Tobin R, et al. FAK activation is required for IGF1R-mediated regulation of EMT, migration, and invasion in mesenchymal triple negative breast cancer cells. Oncotarget. 2015;6:4757–72.PubMedPubMedCentralCrossRef
68.
Kim HJ, Litzenburger BC, Cui X, Delgado DA, Grabiner BC, Lin X, et al. Constitutively active type I insulin-like growth factor receptor causes transformation and xenograft growth of immortalized mammary epithelial cells and is accompanied by an epithelial-to-mesenchymal transition mediated by NF-kappaB and snail. Mol Cell Biol. 2007;27:3165–75.PubMedPubMedCentralCrossRef
69.
Ye X, Tam WL, Shibue T, Kaygusuz Y, Reinhardt F, Ng Eaton E, et al. Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature. 2015;525:256–60.PubMedPubMedCentralCrossRef
70.
Yao C, Su L, Shan J, Zhu C, Liu L, Liu C, et al. IGF/STAT3/NANOG/Slug signaling axis simultaneously controls epithelial-mesenchymal transition and stemness maintenance in colorectal cancer. Stem Cells. 2016;34:820–31.PubMedCrossRef
71.
Tominaga K, Shimamura T, Kimura N, Murayama T, Matsubara D, Kanauchi H, et al. Addiction to the IGF2-ID1-IGF2 circuit for maintenance of the breast cancer stem-like cells. Oncogene. 2017;36:1276–86.PubMedCrossRef
72.
Xu C, Xie D, Yu SC, Yang XJ, He LR, Yang J, et al. β-Catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor signaling and predicts poor prognosis in lung adenocarcinoma. Cancer Res. 2013;73:3181–9.PubMedCrossRef
73.
Chang WW, Lin RJ, Yu J, Chang WY, Fu CH, Lai A, et al. The expression and significance of insulin-like growth factor-1 receptor and its pathway on breast cancer stem/progenitors. Breast Cancer Res. 2013;15:R39.PubMedPubMedCentralCrossRef
74.
Steder M, Alla V, Meier C, Spitschak A, Pahnke J, Fürst K, et al. DNp73 exerts function in metastasis initiation by disconnecting the inhibitory role of EPLIN on IGF1R-AKT/STAT3 signaling. Cancer Cell. 2013;24:512–27.PubMedCrossRef
75.
Meier C, Hardtstock P, Joost S, Alla V, Pützer BM. p73 and IGF1R regulate emergence of aggressive cancer stem-like features via miR-885-5p control. Cancer Res. 2016;76:197–205.PubMedCrossRef
76.
Chen WJ, Ho CC, Chang YL, Chen HY, Lin CA, Ling TY, et al. Cancer-associated fibroblasts regulate the plasticity of lung cancer stemness via paracrine signalling. Nat Commun. 2014;5:3472.PubMedCrossRef
77.
Kim IG, Kim SY, Choi SI, Lee JH, Kim KC, Cho EW. Fibulin-3-mediated inhibition of epithelial-to-mesenchymal transition and self-renewal of ALDH+ lung cancer stem cells through IGF1R signaling. Oncogene. 2014;33:3908–17.PubMedCrossRef
78.
Aleksic T, Chitnis MM, Perestenko OV, et al. Type 1 insulin-like growth factor receptor translocates to the nucleus of human tumor cells. Cancer Res. 2010;70:6412–9.PubMedPubMedCentralCrossRef
79.
Asmane I, Watkin E, Alberti L, Gao S, Thomas PH, Turner GD, et al. Insulin-like growth factor type 1 receptor (IGF-1R) exclusive nuclear staining: a predictive biomarker for IGF-1R monoclonal antibody (Ab) therapy in sarcomas. Eur J Cancer. 2012;48:3027–35.PubMedCrossRef
80.
Aslam MI, Hettmer S, Abraham J, Latocha D, Soundararajan A, Huang ET, et al. Dynamic and nuclear expression of PDGFRα and IGF-1R in alveolar rhabdomyosarcoma. Mol Cancer Res. 2013;11:1303–13.PubMedCrossRef
81.
Sehat B, Tofigh A, Lin Y, Trocmé E, Liljedahl U, Lagergren J, et al. SUMOylation mediates the nuclear translocation and signaling of the IGF-1 receptor. Sci Signal. 2010;3:ra10.PubMedCrossRef
82.
Deng H, Lin Y, Badin M, et al. Over-accumulation of nuclear IGF-1 receptor in tumor cells requires elevated expression of the receptor and the SUMO-conjugating enzyme Ubc9. Biochem Biophys Res Commun. 2011;404:667–71.PubMedCrossRef
83.
Packham S, Warsito D, Lin Y, Vasilcanu D, Strömberg T, Jernberg-Wiklund H, et al. Nuclear translocation of IGF-1R via p150(Glued) and an importin-β/RanBP2-dependent pathway in cancer cells. Oncogene. 2015;34:2227–38.PubMedCrossRef
84.
Guerard M, Robin T, Perron P, Hatat AS, David-Boudet L, Vanwonterghem L, et al. Nuclear translocation of IGF1R by intracellular amphiregulin contributes to the resistance of lung tumour cells to EGFR-TKI. Cancer Lett. 2018;420:146–55.PubMedCrossRef
85.
Sarfstein R, Pasmanik-Chor M, Yeheskel A, Edry L, Shomron N, Warman N, et al. Insulin-like growth factor-I receptor (IGF-IR) translocates to nucleus and autoregulates IGF-IR gene expression in breast cancer cells. J Biol Chem. 2012;287:2766–76.PubMedCrossRef
86.
Aleksic T, Gray N, Wu X, Rieunier G, Osher E, Mills J, et al. Nuclear IGF1R interacts with regulatory regions of chromatin to promote RNA polymerase II recruitment and gene expression associated with advanced tumor stage. Cancer Res. 2018;78:3497–509.PubMedPubMedCentral
87.
88.
Jamwal G, Singh G, Dar MS, Singh P, Bano N, Syed SH, et al. Identification of a unique loss-of-function mutation in IGF1R and a crosstalk between IGF1R and Wnt/β-catenin signaling pathways. Biochim Biophys Acta, Mol Cell Res. 1865;2018:920–31.
89.
Waraky A, Lin Y, Warsito D, Haglund F, Aleem E, Larsson O. Nuclear insulin-like growth factor 1 receptor phosphorylates proliferating cell nuclear antigen and rescues stalled replication forks after DNA damage. J Biol Chem. 2017;292:18227–39.PubMedPubMedCentralCrossRef
90.
Warsito D, Lin Y, Gnirck AC, Sehat B, Larsson O. Nuclearly translocated insulin-like growth factor 1 receptor phosphorylates histone H3 at tyrosine 41 and induces SNAI2 expression via Brg1 chromatin remodeling protein. Oncotarget. 2016;7:42288–302.PubMedPubMedCentralCrossRef
91.
Heskamp S, Boerman OC, Molkenboer-Kuenen JD, Wauters CA, Strobbe LJ, Mandigers CM, et al. Upregulation of IGF-1R expression during neoadjuvant therapy predicts poor outcome in breast cancer patients. PLoS One. 2015;10:e0117745.PubMedPubMedCentralCrossRef
92.
Chitnis MM, Lodhia KA, Aleksic T, Gao S, Protheroe AS, Macaulay VM. IGF-1R inhibition enhances radiosensitivity and delays double-strand break repair by both non-homologous end-joining and homologous recombination. Oncogene. 2014;33:5262–73.PubMedCrossRef
93.
Szymonowicz K, Oeck S, Krysztofiak A, van der Linden J, Iliakis G, Jendrossek V. Restraining Akt1 phosphorylation attenuates the repair of radiation-induced DNA double-strand breaks and reduces the survival of irradiated cancer cells. Int J Mol Sci. 2018;19:2233.PubMedCentralCrossRef
94.
Chen YH, Wang CW, Wei MF, Tzeng YS, Lan KH, Cheng AL, et al. Maintenance BEZ235 treatment prolongs the therapeutic effect of the combination of BEZ235 and radiotherapy for colorectal cancer. Cancers (Basel). 2019;11:1204.CrossRef
95.
Lodhia KA, Gao S, Aleksic T, Esashi F, Macaulay VM. Suppression of homologous recombination sensitizes human tumor cells to IGF-1R inhibition. Int J Cancer. 2015;136:2961–6.PubMedCrossRef
96.
O’Flanagan CH, O’Shea S, Lyons A, Fogarty FM, McCabe N, Kennedy RD, et al. IGF-1R inhibition sensitizes breast cancer cells to ATM-related kinase (ATR) inhibitor and cisplatin. Oncotarget. 2016;7:56826–41.PubMedPubMedCentralCrossRef
97.
Ferté C, Loriot Y, Clémenson C, Commo F, Gombos A, Bibault JE, et al. IGF-1R targeting increases the antitumor effects of DNA-damaging agents in SCLC model: an opportunity to increase the efficacy of standard therapy. Mol Cancer Ther. 2013;12:1213–22.PubMedPubMedCentralCrossRef
98.
Flanigan SA, Pitts TM, Eckhardt SG, Tentler JJ, Tan AC, Thorburn A, et al. The insulin-like growth factor I receptor/insulin receptor tyrosine kinase inhibitor PQIP exhibits enhanced antitumor effects in combination with chemotherapy against colorectal cancer models. Clin Cancer Res. 2010;16:5436–46.PubMedPubMedCentralCrossRef
99.
Zeng X, Zhang H, Oh A, Zhang Y, Yee D. Enhancement of doxorubicin cytotoxicity of human cancer cells by tyrosine kinase inhibition of insulin receptor and type I IGF receptor. Breast Cancer Res Treat. 2012;133:117–26.PubMedCrossRef
100.
Beauchamp MC, Knafo A, Yasmeen A, Carboni JM, Gottardis MM, Pollak MN, et al. BMS-536924 sensitizes human epithelial ovarian cancer cells to the PARP inhibitor, 3-aminobenzamide. Gynecol Oncol. 2009;115:193–8.PubMedCrossRef
101.
Singh RK, Gaikwad SM, Jinager A, Chaudhury S, Maheshwari A, Ray P. IGF-1R inhibition potentiates cytotoxic effects of chemotherapeutic agents in early stages of chemoresistant ovarian cancer cells. Cancer Lett. 2014;354:254–62.PubMedCrossRef
102.
Ramcharan R, Aleksic T, Kamdoum WP, Gao S, Pfister SX, Tanner J, et al. IGF-1R inhibition induces schedule-dependent sensitization of human melanoma to temozolomide. Oncotarget. 2015;6:39877–90.PubMedPubMedCentralCrossRef
103.
Dallas NA, Xia L, Fan F, Gray MJ, Gaur P, van Buren G II, et al. Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition. Cancer Res. 2009;69:1951–7.PubMedPubMedCentralCrossRef
104.
Camblin AJ, Pace EA, Adams S, Curley MD, Rimkunas V, Nie L, et al. Dual Inhibition of IGF-1R and ErbB3 enhances the activity of gemcitabine and Nab-paclitaxel in preclinical models of pancreatic cancer. Clin Cancer Res. 2018;24:2873–85.PubMedCrossRef
105.
Kuhn DJ, Berkova Z, Jones RJ, Woessner R, Bjorklund CC, Ma W, et al. Targeting the insulin-like growth factor-1 receptor to overcome bortezomib resistance in preclinical models of multiple myeloma. Blood. 2012;120:3260–70.PubMedPubMedCentralCrossRef
106.
Vaira V, Lee CW, Goel HL, Bosari S, Languino LR, Altieri DC. Regulation of survivin expression by IGF-1/mTOR signaling. Oncogene. 2007;26:2678–84.PubMedCrossRef
107.
Fox EM, Miller TW, Balko JM, Kuba MG, Sánchez V, Smith RA, et al. A kinome-wide screen identifies the insulin/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer. Cancer Res. 2011;71:6773–84.PubMedPubMedCentralCrossRef
108.
Fox EM, Kuba MG, Miller TW, Davies BR, Arteaga CL. Autocrine IGF-I/insulin receptor axis compensates for inhibition of AKT in ER-positive breast cancer cells with resistance to estrogen deprivation. Breast Cancer Res. 2013;15:R55.PubMedPubMedCentralCrossRef
109.
110.
Chakraborty A, Hatzis C, DiGiovanna MP. Co-targeting the HER and IGF/insulin receptor axis in breast cancer, with triple targeting with endocrine therapy for hormone-sensitive disease. Breast Cancer Res Treat. 2017;163:37–50.PubMedCrossRef
111.
Locke JA, Guns ES, Lehman ML, Ettinger S, Zoubeidi A, Lubik A, et al. Arachidonic acid activation of intratumoral steroid synthesis during prostate cancer progression to castration resistance. Prostate. 2010;70:239–51.PubMed
112.
Lubik AA, Gunter JH, Hollier BG, Ettinger S, Fazli L, Stylianou N, et al. IGF2 increases de novo steroidogenesis in prostate cancer cells. Endocr Relat Cancer. 2013;20:173–86.PubMedCrossRef
113.
Fahrenholtz CD, Beltran PJ, Burnstein KL. Targeting IGF-IR with ganitumab inhibits tumorigenesis and increases durability of response to androgen-deprivation therapy in VCaP prostate cancer xenografts. Mol Cancer Ther. 2013;12:394–404.PubMedPubMedCentralCrossRef
114.
Wang X, Huang Y, Christie A, Bowden M, Lee GS, Kantoff PW, et al. Cabozantinib inhibits abiraterone’s upregulation of IGFIR phosphorylation and enhances its anti-prostate cancer activity. Clin Cancer Res. 2015;21:5578–87.PubMedCrossRef
115.
Nordstrand A, Bergström SH, Thysell E, Bovinder-Ylitalo E, Lerner UH, Widmark A, et al. Inhibition of the insulin-like growth factor-1 receptor potentiates acute effects of castration in a rat model for prostate cancer growth in bone. Clin Exp Metastasis. 2017;34:261–71.PubMedPubMedCentralCrossRef
116.
Jia Y, Zhang Y, Qiao C, Liu G, Zhao Q, Zhou T, et al. IGF-1R and ErbB3/HER3 contribute to enhanced proliferation and carcinogenesis in trastuzumab-resistant ovarian cancer model. Biochem Biophys Res Commun. 2013;436:740–5.PubMedCrossRef
117.
Codony-Servat J, Cuatrecasas M, Asensio E, Montironi C, Martínez-Cardús A, Marín-Aguilera M, et al. Nuclear IGF-1R predicts chemotherapy and targeted therapy resistance in metastatic colorectal cancer. Br J Cancer. 2017;117:1777–86.PubMedPubMedCentralCrossRef
118.
Ma Y, Tang N, Thompson RC, Mobley BC, Clark SW, Sarkaria JN, et al. InsR/IGF1R pathway mediates resistance to EGFR inhibitors in glioblastoma. Clin Cancer Res. 2016;22:1767–76.PubMedCrossRef
119.
Vaquero J, Lobe C, Tahraoui S, Clapéron A, Mergey M, Merabtene F, et al. The IGF2/IR/IGF1R pathway in tumor cells and myofibroblasts mediates resistance to EGFR inhibition in cholangiocarcinoma. Clin Cancer Res. 2018;24:4282–96.PubMedCrossRef
120.
Vitiello PP, Cardone C, Martini G, Ciardiello D, Belli V, Matrone N, et al. Receptor tyrosine kinase-dependent PI3K activation is an escape mechanism to vertical suppression of the EGFR/RAS/MAPK pathway in KRAS-mutated human colorectal cancer cell lines. J Exp Clin Cancer Res. 2019;38:41.PubMedPubMedCentralCrossRef
121.
Sanderson MP, Hofmann MH, Garin-Chesa P, Schweifer N, Wernitznig A, Fischer S, et al. The IGF1R/INSR inhibitor BI 885578 selectively inhibits growth of IGF2-overexpressing colorectal cancer tumors and potentiates the efficacy of anti-VEGF therapy. Mol Cancer Ther. 2017;16:2223–33.PubMedCrossRef
122.
Tovar V, Cornella H, Moeini A, Vidal S, Hoshida Y, Sia D, et al. Tumour initiating cells and IGF/FGF signalling contribute to sorafenib resistance in hepatocellular carcinoma. Gut. 2017;66:530–40.PubMedCrossRef
123.
Merino VF, Cho S, Liang X, Park S, Jin K, Chen Q, et al. Inhibitors of STAT3, β-catenin, and IGF-1R sensitize mouse PIK3CA-mutant breast cancer to PI3K inhibitors. Mol Oncol. 2017;11:552–66.PubMedPubMedCentralCrossRef
124.
Huo X, Liu S, Shao T, Hua H, Kong Q, Wang J, et al. GSK3 protein positively regulates type I insulin-like growth factor receptor through forkhead transcription factors FOXO1/3/4. J Biol Chem. 2014;289:24759–70.PubMedPubMedCentralCrossRef
125.
Scheffold A, Jebaraj BMC, Tausch E, Bloehdorn J, Ghia P, Yahiaoui A, et al. IGF1R as druggable target mediating PI3K-δ inhibitor resistance in a murine model of chronic lymphocytic leukemia. Blood. 2019;134:534–47.PubMedCrossRefPubMedCentral
126.
Leroy C, Ramos P, Cornille K, Bonenfant D, Fritsch C, Voshol H, et al. Activation of IGF1R/p110β/AKT/mTOR confers resistance to α-specific PI3K inhibition. Breast Cancer Res. 2016;18:41.PubMedPubMedCentralCrossRef
127.
Zorea J, Prasad M, Cohen L, Elkabets M, Karabchevsky A. IGF1R upregulation confers resistance to isoform-specific inhibitors of PI3K in PIK3CA-driven ovarian cancer. Cell Death Dis. 2018;9:944.PubMedPubMedCentralCrossRef
128.
Yoon SO, Shin S, Karreth FA, Buel GR, Jedrychowski MP, Plas DR, et al. Focal adhesion- and IGF1R-dependent survival and migratory pathways mediate tumor resistance to mTORC1/2 inhibition. Mol Cell. 2017;67:512–27.PubMedPubMedCentralCrossRef
129.
Lamhamedi-Cherradi SE, Menegaz BA, Ramamoorthy V, Vishwamitra D, Wang Y, Maywald RL, et al. IGF-1R and mTOR blockade: novel resistance mechanisms and synergistic drug combinations for Ewing sarcoma. J Natl Cancer Inst. 2016;108:djw182.PubMedPubMedCentralCrossRef
130.
Benito-Jardón L, Díaz-Martínez M, Arellano-Sánchez N, Vaquero-Morales P, Esparís-Ogando A, Teixidó J. Resistance to MAPK inhibitors in melanoma involves activation of the IGF1R-MEK5-Erk5 pathway. Cancer Res. 2019;79:2244–56.PubMedCrossRef
131.
Strub T, Ghiraldini FG, Carcamo S, Li M, Wroblewska A, Singh R, et al. SIRT6 haploinsufficiency induces BRAFV600E melanoma cell resistance to MAPK inhibitors via IGF signalling. Nat Commun. 2018;9:3440.PubMedPubMedCentralCrossRef
132.
Guenther LM, Dharia NV, Ross L, Conway A, Robichaud AL, Catlett JL 2nd, et al. A combination CDK4/6 and IGF1R inhibitor strategy for Ewing sarcoma. Clin Cancer Res. 2019;25:1343–57.PubMedCrossRef
133.
Isozaki H, Ichihara E, Takigawa N, Ohashi K, Ochi N, Yasugi M, et al. Non-small cell lung cancer cells acquire resistance to the ALK Inhibitor alectinib by activating alternative receptor tyrosine kinases. Cancer Res. 2016;76:1506–16.PubMedCrossRef
134.
George B, George SK, Shi W, Haque A, Shi P, Eskandari G, et al. Dual inhibition of IGF-IR and ALK as an effective strategy to eradicate NPM-ALK+ T-cell lymphoma. J Hematol Oncol. 2019;12:80.PubMedPubMedCentralCrossRef
135.
Lovly CM, McDonald NT, Chen H, Ortiz-Cuaran S, Heukamp LC, Yan Y, et al. Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer. Nat Med. 2014;20:1027–34.PubMedPubMedCentralCrossRef
136.
137.
Li W, Gupta SK, Han W, Kundson RA, Nelson S, Knutson D, et al. Targeting MYC activity in double-hit lymphoma with MYC and BCL2 and/or BCL6 rearrangements with epigenetic bromodomain inhibitors. J Hematol Oncol. 2019;12:73.PubMedPubMedCentralCrossRef
138.
Stuhlmiller TJ, Miller SM, Zawistowski JS, Nakamura K, Beltran AS, Duncan JS, et al. Inhibition of lapatinib-induced kinome reprogramming in ERBB2-positive breast cancer by targeting BET family bromodomains. Cell Rep. 2015;11:390–404.PubMedPubMedCentralCrossRef
139.
Loganathan SN, Tang N, Holler AE, Wang N, Wang J. Targeting the IGF1R/PI3K/AKT pathway sensitizes Ewing sarcoma to BET bromodomain inhibitors. Mol Cancer Ther. 2019;18:929–36.PubMedPubMedCentralCrossRef
140.
141.
Kleer CG, Cao Q, Varambally S, Shen R, Ota I, Tomlins SA, et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc Natl Acad Sci U S A. 2003;100:11606–11.PubMedPubMedCentralCrossRef
142.
143.
144.
Tap WD, Demetri G, Barnette P, Desai J, Kavan P, Tozer R, et al. Phase II study of ganitumab, a fully human anti-type-1 insulin-like growth factor receptor antibody, in patients with metastatic Ewing family tumors or desmoplastic small round cell tumors. J Clin Oncol. 2012;30:1849–56.PubMedCrossRef
145.
Van Cutsem E, Eng C, Nowara E, Swieboda-Sadlej A, Tebbutt NC, Mitchell E, et al. Randomized phase Ib/II trial of rilotumumab or ganitumab with panitumumabversus panitumumab alone in patients with wild-type KRAS metastatic colorectal cancer. Clin Cancer Res. 2014;20:4240–50.PubMedPubMedCentralCrossRef
146.
Fuchs CS, Azevedo S, Okusaka T, Van Laethem J-L, Lipton LR, Riess H, et al. A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. Ann Oncol. 2015;26:921–7.PubMedPubMedCentralCrossRef
147.
Juergens H, Daw NC, Geoerger B, Ferrari S, Villarroel M, Aerts I, et al. Preliminary efficacy of the anti-insulin-like growth factor type 1 receptor antibody figitumumab in patients with refractory Ewing sarcoma. J Clin Oncol. 2011;29:4534–40.PubMedPubMedCentralCrossRef
148.
Olmos D, Postel-Vinay S, Molife LR, Okuno SH, Schuetze SM, Paccagnella ML, et al. Safety, pharmacokinetics, and preliminary activity of the anti-IGF-1R antibody figitumumab (CP-751,871) in patients with sarcoma and Ewing’s sarcoma: a phase 1 expansion cohort study. Lancet Oncol. 2010;11:129–35.PubMedCrossRef
149.
Malempati S, Weigel B, Ingle AM, Ahern CH, Carroll JM, Roberts CT, et al. Phase I/II trial and pharmacokinetic study of cixutumumab in pediatric patients with refractory solid tumors and Ewing sarcoma: a report from the Children’s Oncology Group. J Clin Oncol. 2012;30:256–62.PubMedCrossRef
150.
Schöffski P, Adkins D, Blay JY, Gil T, Elias AD, Rutkowski P, et al. An open-label, phase 2 study evaluating the efficacy and safety of the anti-IGF-1R antibody cixutumumab in patients with previously treated advanced or metastatic soft-tissue sarcoma or Ewing family of tumours. Eur J Cancer. 2013;49:3219–28.PubMedCrossRef
151.
Abdel-Wahab R, Varadhachary GR, Bhosale PR, Wang X, Fogelman DR, Shroff RT, et al. Randomized, phase I/II study of gemcitabine plus IGF-1R antagonist (MK-0646) versus gemcitabine plus erlotinib with and without MK-0646 for advanced pancreatic adenocarcinoma. J Hematol Oncol. 2018;11:71.PubMedPubMedCentralCrossRef
152.
Ramalingam SS, Spigel DR, Chen D, Steins MB, Engelman JA, Schneider CP, et al. Randomized phase II study of erlotinib in combination with placebo or R1507, a monoclonal antibody to insulin-like growth factor-1 receptor, for advanced-stage non-small-cell lung cancer. J Clin Oncol. 2011;29:4574–80.PubMedPubMedCentralCrossRef
153.
Sclafani F, Kim TY, Cunningham D, Kim TW, Tabernero J, Schmoll HJ, et al. A randomized phase II/III study of dalotuzumab in combination with cetuximab and irinotecan in chemorefractory, KRAS wild-type, metastatic colorectal cancer. J Natl Cancer Inst. 2015;107:djv258.PubMedCrossRef
154.
van Maldegem AM, Bovée JV, Peterse EF, Hogendoorn PC, Gelderblom H. Ewing sarcoma: the clinical relevance of the insulin-like growth factor 1 and the poly-ADP-ribose-polymerase pathway. Eur J Cancer. 2016;53:171–80.PubMedCrossRef
155.
Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, Chien AJ, et al. Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with early-stage breast cancer: an analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial. JAMA Oncol. 2020:e196650.
156.
Haluska P, Menefee M, Plimack ER, Rosenberg J, Northfelt D, LaVallee T, et al. Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. Clin Cancer Res. 2014;20:4747–57.PubMedPubMedCentralCrossRef
157.
Iguchi H, Nishina T, Nogami N, Kozuki T, Yamagiwa Y, Yagawa K. Phase I dose-escalation study evaluating safety, tolerability and pharmacokinetics of MEDI-573, a dual IGF-I/II neutralizing antibody, in Japanese patients with advanced solid tumours. Investig New Drugs. 2015;33:194–200.CrossRef
158.
Fassnacht M, Berruti A, Baudin E, Demeure MJ, Gilbert J, Haak H, Kroiss M, et al. Linsitinib (OSI-906) versus placebo for patients with locally advanced or metastatic adrenocortical carcinoma: a double-blind, randomised, phase 3 study. Lancet Oncol. 2015;16:426–35.PubMedCrossRef
159.
Chiappori AA, Otterson GA, Dowlati A, Traynor AM, Horn L, Owonikoko TK, et al. A randomized phase II study of linsitinib (OSI-906) versus topotecan in patients with relapsed small-cell lung cancer. Oncologist. 2016;21:1163–4.PubMedPubMedCentralCrossRef
160.
Bendell JC, Jones SF, Hart L, Spigel DR, Lane CM, Earwood C, et al. A phase Ib study of linsitinib (OSI-906), a dual inhibitor of IGF-1R and IR tyrosine kinase, in combination with everolimus as treatment for patients with refractory metastatic colorectal cancer. Investig New Drugs. 2015;33:187–93.CrossRef
161.
Barata P, Cooney M, Tyler A, Wright J, Dreicer R, Garcia JA. A phase 2 study of OSI-906 (linsitinib, an insulin-like growth factor receptor-1 inhibitor) in patients with asymptomatic or mildly symptomatic (non-opioid requiring) metastatic castrate resistant prostate cancer (CRPC). Investig New Drugs. 2018;36:451–7.CrossRef
162.
von Mehren M, George S, Heinrich MC, Schuetze SM, Yap JT, Yu JQ, et al. Linsitinib (OSI-906) for the treatment of adult and pediatric wild-type gastrointestinal stromal tumors, a SARC phase II study. Clin Cancer Res. 2020;26:1837–45.CrossRef
163.
Aiken R, Axelson M, Harmenberg J, Klockare M, Larsson O, Wassberg C. Phase I clinical trial of AXL1717 for treatment of relapsed malignant astrocytomas: analysis of dose and response. Oncotarget. 2017;8:81501–10.PubMedPubMedCentralCrossRef
164.
Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer. 2013;13:714–26.PubMedCrossRef
165.
Buck E, Gokhale PC, Koujak S, Brown E, Eyzaguirre A, Tao N, et al. Compensatory insulin receptor (IR) activation on inhibition of insulin-like growth factor-1 receptor (IGF-1R): rationale for cotargeting IGF-1R and IR in cancer. Mol Cancer Ther. 2010;9:2652–64.PubMedCrossRef
166.
Rostoker R, Abelson S, Bitton-Worms K, Genkin I, Ben-Shmuel S, Dakwar M, et al. Highly specific role of the insulin receptor in breast cancer progression. Endocr Relat Cancer. 2015;22:145–57.PubMedPubMedCentralCrossRef
167.
Forest A, Amatulli M, Ludwig DL, Damoci CB, Wang Y, Burns CA, et al. Intrinsic resistance to cixutumumab is conferred by distinct isoforms of the insulin receptor. Mol Cancer Res. 2015;13:1615–26.PubMedPubMedCentralCrossRef
168.
Ulanet DB, Ludwig DL, Kahn CR, Hanahan D. Insulin receptor functionally enhances multistage tumor progression and conveys intrinsic resistance to IGF-1R targeted therapy. Proc Natl Acad Sci U S A. 2010;107:10791–8.PubMedPubMedCentralCrossRef
169.
Garofalo C, Manara MC, Nicoletti G, Marino MT, Lollini PL, Astolfi A, et al. Efficacy of and resistance to anti-IGF-1R therapies in Ewing’s sarcoma is dependent on insulin receptor signaling. Oncogene. 2011;30:2730–40.PubMedCrossRef
170.
Seguin L, Desgrosellier JS, Weis SM, Cheresh DA. Integrins and cancer: regulators of cancer stemness, metastasis, and drug resistance. Trends Cell Biol. 2015;25:234–40.PubMedPubMedCentralCrossRef
171.
Saegusa J, Yamaji S, Ieguchi K, Wu CY, Lam KS, Liu FT, et al. The direct binding of insulin-like growth factor-1 (IGF-1) to integrin alphavbeta3 is involved in IGF-1 signaling. J Biol Chem. 2009;284:24106–14.PubMedPubMedCentralCrossRef
172.
Shin DH, Lee HJ, Min HY, Choi SP, Lee MS, Lee JW, et al. Combating resistance to anti-IGFR antibody by targeting the integrin β3-Src pathway. J Natl Cancer Inst. 2013;105:1558–70.PubMedPubMedCentralCrossRef
173.
Wan X, Yeung C, Heske C, Mendoza A, Helman LJ. IGF-1R inhibition activates a YES/SFK bypass resistance pathway: rational basis for co-targeting IGF-1R and Yes/SFK kinase in rhabdomyosarcoma. Neoplasia. 2015;17:358–66.PubMedPubMedCentralCrossRef
174.
Desbois-Mouthon C, Baron A, Blivet-Van Eggelpoël MJ, Fartoux L, Venot C, Bladt F, et al. Insulin-like growth factor-1 receptor inhibition induces a resistance mechanism via the epidermal growth factor receptor/HER3/AKT signaling pathway: rational basis for cotargeting insulin-like growth factor-1 receptor and epidermal growth factor receptor in hepatocellular carcinoma. Clin Cancer Res. 2009;15:5445–56.PubMedCrossRef
175.
Shin DH, Min HY, El-Naggar AK, Lippman SM, Glisson B, Lee HY. Akt/mTOR counteract the antitumor activities of cixutumumab, an anti-insulin-like growth factor I receptor monoclonal antibody. Mol Cancer Ther. 2011;10:2437–48.PubMedPubMedCentralCrossRef
176.
Knowlden JM, Gee JM, Barrow D, Robertson JF, Ellis IO, Nicholson RI, et al. erbB3 recruitment of insulin receptor substrate 1 modulates insulin-like growth factor receptor signalling in oestrogen receptor-positive breast cancer cell lines. Breast Cancer Res. 2011;13:R93.PubMedPubMedCentralCrossRef
177.
Abraham J, Prajapati SI, Nishijo K, Schaffer BS, Taniguchi E, Kilcoyne A, et al. Evasion mechanisms to Igf1r inhibition in rhabdomyosarcoma. Mol Cancer Ther. 2011;10:697–707.PubMedPubMedCentralCrossRef
178.
Potratz JC, Saunders DN, Wai DH, Ng TL, McKinney SE, Carboni JM, et al. Synthetic lethality screens reveal RPS6 and MST1R as modifiers of insulin-like growth factor-1 receptor inhibitor activity in childhood sarcomas. Cancer Res. 2010;70:8770–81.PubMedCrossRef
179.
Huang F, Hurlburt W, Greer A, Reeves KA, Hillerman S, Chang H, et al. Differential mechanisms of acquired resistance to insulin-like growth factor-i receptor antibody therapy or to a small-molecule inhibitor, BMS-754807, in a human rhabdomyosarcoma model. Cancer Res. 2010;70:7221–31.PubMedCrossRef
180.
Heske CM, Yeung C, Mendoza A, Baumgart JT, Edessa LD, Wan X, et al. The role of PDGFR-β activation in acquired resistance to IGF-1R blockade in preclinical models of rhabdomyosarcoma. Transl Oncol. 2016;9:540–7.PubMedPubMedCentralCrossRef
181.
Gvozdenovic A, Boro A, Born W, Muff R, Fuchs B. A bispecific antibody targeting IGF-IR and EGFR has tumor and metastasis suppressive activity in an orthotopic xenograft osteosarcoma mouse model. Am J Cancer Res. 2017;7:1435–49.PubMedPubMedCentral
182.
Zhao H, Desai V, Wang J, Epstein DM, Miglarese M, Buck E. Epithelial-mesenchymal transition predicts sensitivity to the dual IGF-1R/IR inhibitor OSI-906 in hepatocellular carcinoma cell lines. Mol Cancer Ther. 2012;11:503–13.PubMedCrossRef
183.
Nomura S. Identification, friend or foe: vimentin and α-smooth muscle actin in cancer-associated fibroblasts. Ann Surg Oncol. 2019;26:4191–2.PubMedCrossRef
184.
Choi J, Gyamfi J, Jang H, Koo JS. The role of tumor-associated macrophage in breast cancer biology. Histol Histopathol. 2018;33:133–45.PubMed
185.
Lin Y, Xu J, Lan H. Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications. J Hematol Oncol. 2019;12:76.PubMedPubMedCentralCrossRef
186.
187.
Ireland L, Santos A, Ahmed MS, Rainer C, Nielsen SR, Quaranta V, et al. Chemoresistance in pancreatic cancer is driven by stroma-derived insulin-like growth factors. Cancer Res. 2016;76:6851–63.PubMedPubMedCentralCrossRef
188.
Tommelein J, De Vlieghere E, Verset L, Melsens E, Leenders J, Descamps B, et al. Radiotherapy-activated cancer-associated fibroblasts promote tumor progression through paracrine IGF1R activation. Cancer Res. 2018;78:659–70.PubMedCrossRef
189.
Triplett TA, Cardenas KT, Lancaster JN, Hu Z, Selden HJ, Jasso GJ, et al. Endogenous dendritic cells from the tumor microenvironment support T-ALL growth via IGF1R activation. Proc Natl Acad Sci U S A. 2016;113:E1016–25.PubMedPubMedCentralCrossRef
190.
Lee JS, Kang JH, Boo HJ, Hwang SJ, Hong S, Lee SC, et al. STAT3-mediated IGF-2 secretion in the tumour microenvironment elicits innate resistance to anti-IGF-1R antibody. Nat Commun. 2015;6:8499.PubMedCrossRef
191.
Leonetti A, Sharma S, Minari R, Perego P, Giovannetti E, Tiseo M. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br J Cancer. 2019;121:725–37.PubMedCrossRefPubMedCentral
192.
Lee H, Kim N, Yoo YJ, Kim H, Jeong E, Choi S, et al. β-catenin/TCF activity regulates IGF-1R tyrosine kinase inhibitor sensitivity in colon cancer. Oncogene. 2018;37:5466–75.PubMedCrossRef
193.
Oh SC, Sohn BH, Cheong JH, Kim SB, Lee JE, Park KC, et al. Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype. Nat Commun. 2018;9:1777.PubMedPubMedCentralCrossRef
194.
Cohen-Sinai T, Cohen Z, Werner H, Berger R. Identification of BRCA1 as a potential biomarker for insulin-like growth factor-1 receptor targeted therapy in breast cancer. Front Endocrinol (Lausanne). 2017;8:148.CrossRef
195.
Trautmann M, Menzel J, Bertling C, Cyra M, Cyra M, Isfort I, et al. FUS-DDIT3 fusion protein-driven IGF-IR signaling is a therapeutic target in myxoid liposarcoma. Clin Cancer Res. 2017;23:6227–38.PubMedCrossRef
196.
Mancarella C, Casanova-Salas I, Calatrava A, Ventura S, Garofalo C, Rubio-Briones J, et al. ERG deregulation induces IGF-1R expression in prostate cancer cells and affects sensitivity to anti-IGF-1R agents. Oncotarget. 2015;6:16611–22.PubMedPubMedCentralCrossRef
197.
Huang F, Chang H, Greer A, Hillerman S, Reeves KA, Hurlburt W, et al. IRS2 copy number gain, KRAS and BRAF mutation status as predictive biomarkers for response to the IGF-1R/IR inhibitor BMS-754807 in colorectal cancer cell lines. Mol Cancer Ther. 2015;14:620–30.PubMedCrossRef
198.
Patel M, Gomez NC, McFadden AW, Moats-Staats BM, Wu S, Rojas A, et al. PTEN deficiency mediates a reciprocal response to IGFI and mTOR inhibition. Mol Cancer Res. 2014;12:1610–20.PubMedPubMedCentralCrossRef
199.
Wang Q, Wei F, Lv G, Li C, Liu T, Hadjipanayis CG, et al. The association of TP53 mutations with the resistance of colorectal carcinoma to the insulin-like growth factor-1 receptor inhibitor picropodophyllin. BMC Cancer. 2013;13:521.PubMedPubMedCentralCrossRef
200.
Pavlicek A, Lira ME, Lee NV, Ching KA, Ye J, Cao J, et al. Molecular predictors of sensitivity to the insulin-like growth factor 1 receptor inhibitor Figitumumab (CP-751,871). Mol Cancer Ther. 2013;12:2929–39.PubMedCrossRef
201.
McCaffery I, Tudor Y, Deng H, Tang R, Suzuki S, Badola S, et al. Putative predictive biomarkers of survival in patients with metastatic pancreatic adenocarcinoma treated with gemcitabine and ganitumab, an IGF1R inhibitor. Clin Cancer Res. 2013;19:4282–9.PubMedCrossRef
202.
Lee HJ, Pham PC, Hyun SY, Baek B, Kim B, Kim Y, et al. Development of a 4-aminopyrazolo[3,4-d]pyrimidine-based dual IGF1R/Src inhibitor as a novel anticancer agent with minimal toxicity. Mol Cancer. 2018;17:50.PubMedPubMedCentralCrossRef
203.
Kuenzi BM, Remsing Rix LL, Stewart PA, Fang B, Kinose F, Bryant AT, et al. Polypharmacology-based ceritinib repurposing using integrated functional proteomics. Nat Chem Biol. 2017;13:1222–31.PubMedPubMedCentralCrossRef
204.
Russo A, Paret C, Alt F, Burhenne J, Fresnais M, Wagner W, et al. Ceritinib-induced regression of an insulin-like growth factor-driven neuroepithelial brain tumor. Int J Mol Sci. 2019;20:4267.PubMedCentralCrossRef
205.
Vewinger N, Huprich S, Seidmann L, Russo A, Alt F, Bender H, et al. IGF1R is a potential new therapeutic target for HGNET-BCOR brain tumor patients. Int J Mol Sci. 2019;20:3027.PubMedCentralCrossRef
206.
Reuveni H, Flashner-Abramson E, Steiner L, Makedonski K, Song R, Shir A, et al. Therapeutic destruction of insulin receptor substrates for cancer treatment. Cancer Res. 2013;73:4383–94.PubMedPubMedCentralCrossRef
207.
Ibuki N, Ghaffari M, Reuveni H, Pandey M, Fazli L, Azuma H, et al. The tyrphostin NT157 suppresses insulin receptor substrates and augments therapeutic response of prostate cancer. Mol Cancer Ther. 2014;13:2827–39.PubMedCrossRef
208.
Yang Y, Chan JY, Temiz NA, Yee D. Insulin receptor substrate suppression by the tyrphostin NT157 inhibits responses to insulin-like growth factor-I and insulin in breast cancer cells. Horm Cancer. 2018;9:371–82.PubMedPubMedCentralCrossRef
209.
Janku F, Huang HJ, Angelo LS, Kurzrock R. A kinase-independent biological activity for insulin growth factor-1 receptor (IGF-1R): implications for inhibition of the IGF-1R signal. Oncotarget. 2013;4:463–73.PubMedPubMedCentralCrossRef
210.
Pian L, Wen X, Kang L, Li Z, Nie Y, Du Z, et al. Targeting the IGF1R pathway in breast cancer using antisense lncRNA-mediated promoter cis competition. Mol Ther Nucleic Acids. 2018;12:105–17.PubMedPubMedCentralCrossRef
211.
Metadata
Title
Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy
Authors
Hui Hua
Qingbin Kong
Jie Yin
Jin Zhang
Yangfu Jiang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2020
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-020-00904-3

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