Generic placeholder image

Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Different Roles of the Insulin-like Growth Factor (IGF) Axis in Non-small Cell Lung Cancer

Author(s): Xiongye Xu, Yanli Qiu, Simin Chen, Shuaishuai Wang, Ruifu Yang, Baomo Liu, Yufei Li, Jiating Deng, Yan Su, Ziying Lin, Jincui Gu, Shaoli Li, Lixia Huang* and Yanbin Zhou*

Volume 28, Issue 25, 2022

Published on: 27 July, 2022

Page: [2052 - 2064] Pages: 13

DOI: 10.2174/1381612828666220608122934

Price: $65


Non-small cell lung cancer (NSCLC) remains one of the deadliest malignant diseases, with high incidence and mortality worldwide. The insulin-like growth factor (IGF) axis, consisting of IGF-1, IGF-2, related receptors (IGF-1R, -2R), and high-affinity binding proteins (IGFBP 1-6), is associated with promoting fetal development, tissue growth, and metabolism. Emerging studies have also identified the role of the IGF axis in NSCLC, including cancer growth, invasion, and metastasis. Upregulation of IGE-1 and IGF-2, overexpression of IGF-1R, and dysregulation of downstream signaling molecules involved in the PI-3K/Akt and MAPK pathways jointly increase the risk of cancer growth and migration in NSCLC. At the genetic level, some noncoding RNAs could influence the proliferation and differentiation of tumor cells through the IGF signaling pathway. The resistance to some promising drugs might be partially attributed to the IGF axis. Therapeutic strategies targeting the IGF axis have been evaluated, and some have shown promising efficacy. In this review, we summarize the biological roles of the IGF axis in NSCLC, including the expression and prognostic significance of the related components, noncoding RNA regulation, involvement in drug resistance, and therapeutic application. This review offers a comprehensive understanding of NSCLC and provides insightful ideas for future research.

Keywords: NSCLC, IGF-1, IGF-2, IGF-1R, IGF-binding proteins, signaling, treatment, cancer therapeutic resistance.

Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71(3): 209-49.
[] [PMID: 33538338]
Herbst RS, Morgensztern D, Boshoff C. The biology and management of non-small cell lung cancer. Nature 2018; 553(7689): 446-54.
[] [PMID: 29364287]
Rodak O, Peris-Díaz MD, Olbromski M, Podhorska-Okołów M, Dzięgiel P. Current landscape of non-small cell lung cancer: epidemiology, histological classification, targeted therapies, and immunotherapy. Cancers (Basel) 2021; 13(18): 13.
[] [PMID: 34572931]
Grimberg A, Cohen P. Role of insulin-like growth factors and their binding proteins in growth control and carcinogenesis. J Cell Physiol 2000; 183(1): 1-9.
[<1::AID-JCP1>3.0.CO;2-J] [PMID: 10699960]
Chen YM, Qi S, Perrino S, Hashimoto M, Brodt P. Targeting the IGF-axis for cancer therapy: development and validation of an IGF-trap as a potential drug. Cells 2020; 9(5): 9.
[] [PMID: 32365498]
Ren J, Anversa P. The insulin-like growth factor I system: Physiological and pathophysiological implication in cardiovascular diseases associated with metabolic syndrome. Biochem Pharmacol 2015; 93(4): 409-17.
[] [PMID: 25541285]
AsghariHanjani N, Vafa M. The role of IGF-1 in obesity, cardiovascular disease, and cancer. Med J Islam Repub Iran 2019; 33: 56.
[] [PMID: 31456980]
Crosby P, Hamnett R, Putker M, et al. Insulin/IGF-1 drives PERIOD synthesis to entrain circadian rhythms with feeding time. Cell 2019; 177(4): 896-909.e20.
[] [PMID: 31030999]
Lu C, Shan Z, Hong J, Yang L. MicroRNA-92a promotes epithelial-mesenchymal transition through activation of PTEN/PI3K/AKT signaling pathway in non-small cell lung cancer metastasis. Int J Oncol 2017; 51(1): 235-44.
[] [PMID: 28534966]
Li W, Ma J, Ma Q, et al. Resveratrol inhibits the epithelial-mesenchymal transition of pancreatic cancer cells via suppression of the PI-3K/Akt/NF-κB pathway. Curr Med Chem 2013; 20(33): 4185-94.
[] [PMID: 23992306]
Khateeb J, Fuchs E, Khamaisi M. Diabetes and lung disease: a neglected relationship. Rev Diabet Stud 2019; 15(1): 1-15.
[] [PMID: 30489598]
Wang M, Yang Y, Liao Z. Diabetes and cancer: Epidemiological and biological links. World J Diabetes 2020; 11(6): 227-38.
[] [PMID: 32547697]
Duguay SJ, Jin Y, Stein J, Duguay AN, Gardner P, Steiner DF. Post-translational processing of the insulin-like growth factor-2 precursor. Analysis of O-glycosylation and endoproteolysis. J Biol Chem 1998; 273(29): 18443-51.
[] [PMID: 9660813]
Livingstone C. IGF2 and cancer. Endocr Relat Cancer 2013; 20(6): R321-39.
[] [PMID: 24080445]
Liu X, Chen X, Zeng K, et al. DNA-methylation-mediated silencing of miR-486-5p promotes colorectal cancer proliferation and migration through activation of PLAGL2/IGF2/β-catenin signal pathways. Cell Death Dis 2018; 9(10): 1037.
[] [PMID: 30305607]
Greenall SA, Bentley JD, Pearce LA, et al. Biochemical characterization of individual human glycosylated pro-insulin-like growth factor (IGF)-II and big-IGF-II isoforms associated with cancer. J Biol Chem 2013; 288(1): 59-68.
[] [PMID: 23166326]
Holly JMP, Biernacka K, Perks CM. The neglected insulin: IGF-II, a metabolic regulator with implications for diabetes, obesity, and cancer. Cells 2019; 8(10): 8.
[] [PMID: 31590432]
Peruzzi F, Prisco M, Dews M, et al. Multiple signaling pathways of the insulin-like growth factor 1 receptor in protection from apoptosis. Mol Cell Biol 1999; 19(10): 7203-15.
[] [PMID: 10490655]
Mutgan AC, Besikcioglu HE, Wang S, Friess H, Ceyhan GO, Demir IE. Insulin/IGF-driven cancer cell-stroma crosstalk as a novel therapeutic target in pancreatic cancer. Mol Cancer 2018; 17(1): 66.
[] [PMID: 29475434]
Iams WT, Lovly CM. Molecular pathways: clinical applications and future direction of insulin-like growth factor-1 receptor pathway blockade. Clin Cancer Res 2015; 21(19): 4270-7.
[] [PMID: 26429980]
Li J, Choi E, Yu H, Bai XC. Structural basis of the activation of type 1 insulin-like growth factor receptor. Nat Commun 2019; 10(1): 4567.
[] [PMID: 31594955]
Crudden C, Song D, Cismas S, et al. Below the surface: IGF-1R therapeutic targeting and its endocytic journey. Cells 2019; 8(10): 8.
[] [PMID: 31600876]
Potalitsyn P, Selicharová I, Sršeň K, et al. A radioligand binding assay for the insulin-like growth factor 2 receptor. PLoS One 2020; 15(9): e0238393.
[] [PMID: 32877466]
Martin-Kleiner I, Gall Troselj K. Mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) in carcinogenesis. Cancer Lett 2010; 289(1): 11-22.
[] [PMID: 19646808]
Torrente Y, Bella P, Tripodi L, Villa C, Farini A. Role of insulin-like growth factor receptor 2 across muscle homeostasis: implications for treating muscular dystrophy. Cells 2020; 9(2): 9.
[] [PMID: 32075092]
Bach LA. IGF-binding proteins. J Mol Endocrinol 2018; 61(1): T11-28.
[] [PMID: 29255001]
Bach LA, Headey SJ, Norton RS. IGF-binding proteins--the pieces are falling into place. Trends Endocrinol Metab 2005; 16(5): 228-34.
[] [PMID: 15935690]
Jin L, Shen F, Weinfeld M, Sergi C. Insulin Growth Factor Binding Protein 7 (IGFBP7)-related cancer and IGFBP3 and IGFBP7 crosstalk. Front Oncol 2020; 10: 727.
[] [PMID: 32500027]
Lin YW, Weng XF, Huang BL, Guo HP, Xu YW, Peng YH. IGFBP-1 in cancer: Expression, molecular mechanisms, and potential clinical implications. Am J Transl Res 2021; 13(3): 813-32.
[PMID: 33841624]
Li T, Forbes ME, Fuller GN, Li J, Yang X, Zhang W. IGFBP2: Integrative hub of developmental and oncogenic signaling network. Oncogene 2020; 39(11): 2243-57.
[] [PMID: 31925333]
Cai Q, Dozmorov M, Oh Y. IGFBP-3/IGFBP-3 receptor system as an anti-tumor and anti-metastatic signaling in cancer. Cells 2020; 9(5): 9.
[] [PMID: 32443727]
Shrivastav SS, Bhardwaj A, Pathak KA, Shrivastav A. Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3): unraveling the role in mediating IGF-Independent effects within the cell. Front Cell Dev Biol 2020; 8: 286.
[] [PMID: 32478064]
Hermani A, Shukla A, Medunjanin S, Werner H, Mayer D. Insulin-like growth factor binding protein-4 and -5 modulate ligand-dependent estrogen receptor-α activation in breast cancer cells in an IGF-independent manner. Cell Signal 2013; 25(6): 1395-402.
[] [PMID: 23499909]
Moreno MJ, Ball M, Rukhlova M, et al. IGFBP-4 anti-angiogenic and anti-tumorigenic effects are associated with anti-cathepsin B activity. Neoplasia 2013; 15(5): 554-67.
[] [PMID: 23633927]
Hwang JR, Cho YJ, Lee Y, et al. The C-terminus of IGFBP-5 suppresses tumor growth by inhibiting angiogenesis. Sci Rep 2016; 6(1): 39334.
[] [PMID: 28008951]
Liso A, Capitanio N, Gerli R, Conese M. From fever to immunity: A new role for IGFBP-6? J Cell Mol Med 2018; 22(10): 4588-96.
[] [PMID: 30117676]
Qi L, Liu F, Zhang F, et al. lncRNA NEAT1 competes against let-7a to contribute to non-small cell lung cancer proliferation and metastasis. Biomed Pharmacother 2018; 103: 1507-15.
[] [PMID: 29864936]
Tang H, Bai Y, Pan G, et al. Interleukin-6 and insulin-like growth factor-1 synergistically promote the progression of NSCLC. Autoimmunity 2018; 51(8): 399-407.
[] [PMID: 30604632]
Pal S, Yadav P, Sainis KB, Shankar BS. TNF-α and IGF-1 differentially modulate ionizing radiation responses of lung cancer cell lines. Cytokine 2018; 101: 89-98.
[] [PMID: 27344406]
Kim JS, Kim ES, Liu D, et al. Prognostic implications of tumoral expression of insulin like growth factors 1 and 2 in patients with non-small-cell lung cancer. Clin Lung Cancer 2014; 15(3): 213-21.
[] [PMID: 24485233]
Kotsantis I, Economopoulou P, Psyrri A, et al. Prognostic significance of IGF-1 signalling pathway in patients with advanced non-small cell lung cancer. Anticancer Res 2019; 39(8): 4185-90.
[] [PMID: 31366504]
Zhang ZF, Pei BX, Wang AL, et al. Expressions of CLDN1 and insulin-like growth factor 2 are associated with poor prognosis in stage N2 non-small cell lung cancer. Chin Med J (Engl) 2013; 126(19): 3668-74.
[PMID: 24112161]
Agulló-Ortuño MT, Díaz-García CV, Agudo-López A, et al. Relevance of insulin-like growth factor 1 receptor gene expression as a prognostic factor in non-small-cell lung cancer. J Cancer Res Clin Oncol 2015; 141(1): 43-53.
[] [PMID: 25081930]
Gately K, Forde L, Cuffe S, et al. High coexpression of both EGFR and IGF1R correlates with poor patient prognosis in resected non-small-cell lung cancer. Clin Lung Cancer 2014; 15(1): 58-66.
[] [PMID: 24210543]
Vilmar A, Santoni-Rugiu E, Cillas JG, Huarriz M, Sørensen JB. Insulin-like growth factor receptor 1 mRNA expression as a prognostic marker in advanced non-small cell lung cancer. Anticancer Res 2014; 34(6): 2991-6.
[PMID: 24922664]
Xu J, Bie F, Wang Y, Chen X, Yan T, Du J. Prognostic value of IGF-1R in lung cancer: A PRISMA-compliant meta-analysis. Medicine (Baltimore) 2019; 98(19): e15467.
[] [PMID: 31083179]
Al-Saad S, Richardsen E, Kilvaer TK, et al. The impact of MET, IGF-1, IGF1R expression and EGFR mutations on survival of patients with non-small-cell lung cancer. PLoS One 2017; 12(7): e0181527.
[] [PMID: 28742836]
Liu TC, Hsieh MJ, Liu MC, Chiang WL, Tsao TC, Yang SF. The clinical significance of the insulin-like growth factor-1 receptor polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation. Int J Mol Sci 2016; 17(5): 17.
[] [PMID: 27213344]
Reinmuth N, Kloos S, Warth A, et al. Insulin-like growth factor 1 pathway mutations and protein expression in resected non-small cell lung cancer. Hum Pathol 2014; 45(6): 1162-8.
[] [PMID: 24745618]
Tian Z, Yao G, Song H, Zhou Y, Geng J. IGF2R expression is associated with the chemotherapy response and prognosis of patients with advanced NSCLC. Cell Physiol Biochem 2014; 34(5): 1578-88.
[] [PMID: 25402559]
Piper AJ, Clark JL, Mercado-Matos J, et al. Insulin Receptor Substrate-1 (IRS-1) and IRS-2 expression levels are associated with prognosis in non-small cell lung cancer (NSCLC). PLoS One 2019; 14(8): e0220567.
[] [PMID: 31393907]
Dong J, Zeng Y, Zhang P, et al. Serum IGFBP2 level is a new candidate biomarker of severe malnutrition in advanced lung cancer. Nutr Cancer 2020; 72(5): 858-63.
[] [PMID: 32286106]
Guo C, Lu H, Gao W, et al. Insulin-like growth factor binding protein-2 level is increased in blood of lung cancer patients and associated with poor survival. PLoS One 2013; 8(9): e74973.
[] [PMID: 24069370]
Wang J, Hu ZG, Li D, Xu JX, Zeng ZG. Gene expression and prognosis of insulin-like growth factor-binding protein family members in non-small cell lung cancer. Oncol Rep 2019; 42(5): 1981-95.
[] [PMID: 31545451]
Wang Z, Wang Z, Liang Z, et al. Expression and clinical significance of IGF-1, IGFBP-3, and IGFBP-7 in serum and lung cancer tissues from patients with non-small cell lung cancer. OncoTargets Ther 2013; 6: 1437-44.
[PMID: 24204158]
Cai D, Xu Y, Ding R, et al. Extensive serum biomarker analysis in patients with non-small-cell lung carcinoma. Cytokine 2020; 126: 154868.
[] [PMID: 31629110]
Suzuki M, Shiraishi K, Eguchi A, et al. Aberrant methylation of LINE-1, SLIT2, MAL and IGFBP7 in non-small cell lung cancer. Oncol Rep 2013; 29(4): 1308-14.
[] [PMID: 23381221]
Li W, Sun D, Lv Z, et al. Insulin-like growth factor binding protein-4 inhibits cell growth, migration and invasion, and downregulates COX-2 expression in A549 lung cancer cells. Cell Biol Int 2017; 41(4): 384-91.
[] [PMID: 28150906]
Xiao Y, Zhu S, Yin W, Liu X, Hu Y. IGFBP-4 expression is adversely associated with lung cancer prognosis. Oncol Lett 2017; 14(6): 6876-80.
[] [PMID: 29163706]
Kelley KM, Oh Y, Gargosky SE, et al. Insulin-like growth factor-binding proteins (IGFBPs) and their regulatory dynamics. Int J Biochem Cell Biol 1996; 28(6): 619-37.
[] [PMID: 8673727]
Le HT, Lee HJ, Cho J, et al. Insulin-like growth factor binding protein-3 exerts its anti-metastatic effect in aerodigestive tract cancers by disrupting the protein stability of vimentin. Cancers (Basel) 2021; 13(5): 13.
[] [PMID: 33801272]
Oh SH, Lee OH, Schroeder CP, et al. Antimetastatic activity of insulin-like growth factor binding protein-3 in lung cancer is mediated by insulin-like growth factor-independent urokinase-type plasminogen activator inhibition. Mol Cancer Ther 2006; 5(11): 2685-95.
[] [PMID: 17121915]
Kim JH, Choi DS, Lee OH, Oh SH, Lippman SM, Lee HY. Antiangiogenic antitumor activities of IGFBP-3 are mediated by IGF-independent suppression of Erk1/2 activation and EGR-1-mediated transcriptional events. Blood 2011; 118(9): 2622-31.
[] [PMID: 21551235]
Jin Q, Lee HJ, Min HY, et al. Transcriptional and posttranslational regulation of insulin-like growth factor binding protein-3 by Akt3. Carcinogenesis 2014; 35(10): 2232-43.
[] [PMID: 24942865]
Sun Y, Ai X, Shen S, Gu L, Lu S. Detection and correlation analysis of serum cytokines in non-small-cell lung cancer patients with bone and non-bone metastases. Patient Prefer Adherence 2015; 9: 1165-9.
[PMID: 26316721]
Yang L, Li J, Fu S, et al. Up-regulation of insulin-like growth factor binding protein-3 is associated with brain metastasis in lung adenocarcinoma. Mol Cells 2019; 42(4): 321-32.
[PMID: 31085806]
Ghafouri-Fard S, Abak A, Mohaqiq M, Shoorei H, Taheri M. The interplay between non-coding rnas and insulin-like growth factor signaling in the pathogenesis of neoplasia. Front Cell Dev Biol 2021; 9: 634512.
[] [PMID: 33768092]
Lu J, Zhan Y, Feng J, Luo J, Fan S. MicroRNAs associated with therapy of non-small cell lung cancer. Int J Biol Sci 2018; 14(4): 390-7.
[] [PMID: 29725260]
Wen XP, Ma HL, Zhao LY, Zhang W, Dang CX. MiR-30a suppresses non-small cell lung cancer progression through AKT signaling pathway by targeting IGF1R. Cell Mol Biol 2015; 61(2): 78-85.
[PMID: 26025408]
Zhou Y, Li S, Li J, Wang D, Li Q. Effect of microRNA-135a on cell proliferation, migration, invasion, apoptosis and tumor angiogenesis through the IGF-1/pi3k/akt signaling pathway in non-small cell lung cancer. Cell Physiol Biochem 2017; 42(4): 1431-46.
[] [PMID: 28715819]
Wang J, Shi C, Wang J, Cao L, Zhong L, Wang D. MicroRNA-320a is downregulated in non-small cell lung cancer and suppresses tumor cell growth and invasion by directly targeting insulin-like growth factor 1 receptor. Oncol Lett 2017; 13(5): 3247-52.
[] [PMID: 28521431]
Zhou F, Nie L, Feng D, Guo S, Luo R. MicroRNA-379 acts as a tumor suppressor in non-small cell lung cancer by targeting the IGF-1R-mediated AKT and ERK pathways. Oncol Rep 2017; 38(3): 1857-66.
[] [PMID: 28731178]
Zhou G, Xie J, Gao Z, Yao W. MicroRNA-877 inhibits cell proliferation and invasion in non-small cell lung cancer by directly targeting IGF-1R. Exp Ther Med 2019; 18(2): 1449-57.
[] [PMID: 31316632]
Liu J, Jia Y, Jia L, Li T, Yang L, Zhang G. MicroRNA 615-3p inhibits the tumor growth and metastasis of NSCLC via inhibiting IGF2. Oncol Res 2019; 27(2): 269-79.
[] [PMID: 29562959]
Wang M, Shi J, Jiang H, Xu K, Huang Z. Circ_0014130 participates in the proliferation and apoptosis of nonsmall cell lung cancer cells via the miR-142-5p/IGF-1 axis. Cancer Biother Radiopharm 2020; 35(3): 233-40.
[] [PMID: 31916848]
Tian F, Wang Y, Xiao Z, Zhu X. Circular RNA CircHIPK3 Promotes NCI-H1299 and NCI-H2170 Cell Proliferation through miR-379 and its Target IGF1. Zhongguo Fei Ai Za Zhi 2017; 20(7): 459-67.
[PMID: 28738961]
Li Z, Lu Q, Zhu D, Han Y, Zhou X, Ren T. Lnc-SNHG1 may promote the progression of non-small cell lung cancer by acting as a sponge of miR-497. Biochem Biophys Res Commun 2018; 506(3): 632-40.
[] [PMID: 30454699]
Liu Y, Lin X, Zhou S, Zhang P, Shao G, Yang Z. Long noncoding RNA HOXA-AS2 promotes non-small cell lung cancer progression by regulating miR-520a-3p. Biosci Rep 2019; 39(5): 39.
[] [PMID: 31064819]
Zheng FX, Wang XQ, Zheng WX, Zhao J. Long noncoding RNA HOXA-AS2 promotes cell migration and invasion via upregulating IGF-2 in non-small cell lung cancer as an oncogene. Eur Rev Med Pharmacol Sci 2019; 23(11): 4793-9.
[PMID: 31210310]
Dong Y, Huo X, Sun R, Liu Z, Huang M, Yang S. LncRNA Gm15290 promotes cell proliferation and invasion in non-small cell lung cancer through directly interacting with and suppressing the tumor suppressor miR-615-5p. Biosci Rep 2018; 38(5): BSR20181150.
[] [PMID: 28474572]
Gao S, Lin Z, Li C, et al. lncINS-IGF2 promotes cell proliferation and migration by promoting G1/S transition in lung cancer. Technol Cancer Res Treat 2019; 18: 1533033818823029.
[] [PMID: 30803359]
Sanderson MP, Hofmann MH, Garin-Chesa P, 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(10): 2223-33.
[] [PMID: 28729397]
Vincent EE, Elder DJ, Curwen J, Kilgour E, Hers I, Tavaré JM. Targeting non-small cell lung cancer cells by dual inhibition of the insulin receptor and the insulin-like growth factor-1 receptor. PLoS One 2013; 8(6): e66963.
[] [PMID: 23826179]
Ekman S, Frödin JE, Harmenberg J, et al. Clinical Phase I study with an Insulin-like Growth Factor-1 receptor inhibitor: Experiences in patients with squamous non-small cell lung carcinoma. Acta Oncol 2011; 50(3): 441-7.
[] [PMID: 20698809]
Ekman S, Harmenberg J, Frödin JE, et al. A novel oral insulin-like growth factor-1 receptor pathway modulator and its implications for patients with non-small cell lung carcinoma: A phase I clinical trial. Acta Oncol 2016; 55(2): 140-8.
[] [PMID: 26161618]
Holgersson G, Bergström S, Harmenberg J, et al. A phase I pilot study of the insulin-like growth factor 1 receptor pathway modulator AXL1717 in combination with gemcitabine HCl and carboplatin in previously untreated, locally advanced, or metastatic non-small cell lung cancer. Med Oncol 2015; 32(4): 129.
[] [PMID: 25794491]
Bergqvist M, Holgersson G, Bondarenko I, et al. Phase II randomized study of the IGF-1R pathway modulator AXL1717 compared to docetaxel in patients with previously treated, locally advanced or metastatic non-small cell lung cancer. Acta Oncol 2017; 56(3): 441-7.
[] [PMID: 27882820]
Ciuleanu TE, Ahmed S, Kim JH, et al. Randomised Phase 2 study of maintenance linsitinib (OSI-906) in combination with erlotinib compared with placebo plus erlotinib after platinum-based chemotherapy in patients with advanced non-small cell lung cancer. Br J Cancer 2017; 117(6): 757-66.
[] [PMID: 28772281]
Leighl NB, Rizvi NA, de Lima LG Jr, et al. Phase 2 study of erlotinib in combination with linsitinib (OSI-906) or placebo in chemotherapy-naive patients with non-small-cell lung cancer and activating epidermal growth factor receptor mutations. Clin Lung Cancer 2017; 18(1): 34-42.e2.
[] [PMID: 27686971]
Macaulay VM, Middleton MR, Eckhardt SG, et al. Phase I dose-escalation study of linsitinib (OSI-906) and erlotinib in patients with advanced solid tumors. Clin Cancer Res 2016; 22(12): 2897-907.
[] [PMID: 26831715]
Yeo CD, Kim YA, Lee HY, et al. Inhibiting IGF-1R attenuates cell proliferation and VEGF production in IGF-1R over-expressing EGFR mutant non-small cell lung cancer cells. Exp Lung Res 2017; 43(1): 29-37.
[] [PMID: 28394654]
Lovly CM, McDonald NT, Chen H, et al. Rationale for co-targeting IGF-1R and ALK in ALK fusion-positive lung cancer. Nat Med 2014; 20(9): 1027-34.
[] [PMID: 25173427]
Wilson C, Nimick M, Nehoff H, Ashton JC. ALK and IGF-1R as independent targets in crizotinib resistant lung cancer. Sci Rep 2017; 7(1): 13955.
[] [PMID: 29066738]
Zhou Y, Zhang Z, Wang N, et al. Suppressor of cytokine signalling-2 limits IGF1R-mediated regulation of epithelial-mesenchymal transition in lung adenocarcinoma. Cell Death Dis 2018; 9(4): 429.
[] [PMID: 29559623]
Lee HJ, Pham PC, Hyun SY, 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(1): 50.
[] [PMID: 29455661]
Lee HJ, Pham PC, Pei H, et al. Development of the phenylpyrazolo[3,4-d]pyrimidine-based, insulin-like growth factor receptor/Src/AXL-targeting small molecule kinase inhibitor. Theranostics 2021; 11(4): 1918-36.
[] [PMID: 33408789]
Goto Y, Sekine I, Tanioka M, et al. Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer. Invest New Drugs 2012; 30(4): 1548-56.
[] [PMID: 21748299]
Calvo E, Soria JC, Ma WW, et al. A phase I clinical trial and independent patient-derived xenograft study of combined targeted treatment with dacomitinib and figitumumab in advanced solid tumors. Clin Cancer Res 2017; 23(5): 1177-85.
[] [PMID: 27733479]
Langer CJ, Novello S, Park K, et al. Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer. J Clin Oncol 2014; 32(19): 2059-66.
[] [PMID: 24888810]
Argiris A, Lee JW, Stevenson J, et al. Phase II randomized trial of carboplatin, paclitaxel, bevacizumab with or without cixutumumab (IMC-A12) in patients with advanced non-squamous, non-small-cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E3508). Ann Oncol 2017; 28(12): 3037-43.
[] [PMID: 28950351]
Jeong I, Kang SK, Kwon WS, et al. Regulation of proliferation and invasion by the IGF signalling pathway in Epstein-Barr virus-positive gastric cancer. J Cell Mol Med 2018; 22(12): 5899-908.
[] [PMID: 30247804]
Gui Y, Aguilar-Mahecha A, Krzemien U, et al. Metastatic breast carcinoma-associated fibroblasts have enhanced protumorigenic properties related to increased IGF2 expression. Clin Cancer Res 2019; 25(23): 7229-42.
[] [PMID: 31515454]
Yamaoka T, Ohmori T, Ohba M, et al. Acquired resistance mechanisms to combination met-TKI/EGFR-TKI exposure in met-amplified EGFR-TKI-resistant lung adenocarcinoma harboring an activating EGFR mutation. Mol Cancer Ther 2016; 15(12): 3040-54.
[] [PMID: 27612490]
Park JH, Choi YJ, Kim SY, et al. Activation of the IGF1R pathway potentially mediates acquired resistance to mutant-selective 3rd-generation EGF receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer. Oncotarget 2016; 7(16): 22005-15.
[] [PMID: 26980747]
Moran T, Felip E, Keedy V, et al. Activity of dalotuzumab, a selective anti-IGF1R antibody, in combination with erlotinib in unselected patients with Non-small-cell lung cancer: A phase I/II randomized trial. Exp Hematol Oncol 2014; 3(1): 26.
[] [PMID: 25414803]
Bost F, Decoux-Poullot AG, Tanti JF, Clavel S. Energy disruptors: Rising stars in anticancer therapy? Oncogenesis 2016; 5(1): e188.
[] [PMID: 26779810]
Sun L, Liu X, Fu H, Zhou W, Zhong D. 2-Deoxyglucose suppresses ERK phosphorylation in LKB1 and Ras wild-type non-small cell lung cancer cells. PLoS One 2016; 11(12): e0168793.
[] [PMID: 28033353]
Liu F, Liu Y, Liu X, et al. Inhibition of IGF1R enhances 2-deoxyglucose in the treatment of non-small cell lung cancer. Lung Cancer 2018; 123: 36-43.
[] [PMID: 30089593]
Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 2014; 511(7511): 543-50.
[] [PMID: 25079552]
Kerr EM, Martins CP. Metabolic rewiring in mutant Kras lung cancer. FEBS J 2018; 285(1): 28-41.
[] [PMID: 28570035]
Xu H, Lee MS, Tsai PY, et al. Ablation of insulin receptor substrates 1 and 2 suppresses Kras-driven lung tumorigenesis. Proc Natl Acad Sci USA 2018; 115(16): 4228-33.
[] [PMID: 29610318]
Tang Q, Wu J, Zheng F, Hann SS, Chen Y. Emodin increases expression of insulin-like growth factor binding protein 1 through activation of MEK/ERK/AMPKα and interaction of PPARγ and Sp1 in lung cancer. Cell Physiol Biochem 2017; 41(1): 339-57.
[] [PMID: 28214826]
Liu CH, Bao HG, Ge YL, Wang SK, Shen Y, Xu L. Celecoxib inhibits insulin-like growth factor 1 induced growth and invasion in non-small cell lung cancer. Oncol Lett 2013; 5(6): 1943-7.
[] [PMID: 23833672]
Wei W, Wang L, Xu L, Zeng J. Anticancer mechanism of breviscapine in non-small cell lung cancer A549 cells acts via ROS-mediated upregulation of IGFBP4. J Thorac Dis 2021; 13(4): 2475-85.
[] [PMID: 34012594]
Planchard D, Popat S, Kerr K, et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2018; 29: iv192-237.
Min HY, Lee HY. Mechanisms of resistance to chemotherapy in non-small cell lung cancer. Arch Pharm Res 2021; 44(2): 146-64.
[] [PMID: 33608812]
Wu X, Wu Q, Zhou X, Huang J. SphK1 functions downstream of IGF-1 to modulate IGF-1-induced EMT, migration and paclitaxel resistance of A549 cells: A preliminary in vitro study. J Cancer 2019; 10(18): 4264-9.
[] [PMID: 31413745]
Wang YA, Sun Y, Palmer J, et al. IGFBP3 modulates lung tumorigenesis and cell growth through IGF1 signaling. Mol Cancer Res 2017; 15(7): 896-904.
[] [PMID: 28330997]
Cortés-Sempere M, de Miguel MP, Pernía O, et al. IGFBP-3 methylation-derived deficiency mediates the resistance to cisplatin through the activation of the IGFIR/Akt pathway in non-small cell lung cancer. Oncogene 2013; 32(10): 1274-83.
[] [PMID: 22543588]
Wu F, Yang J, Liu J, et al. Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer. Signal Transduct Target Ther 2021; 6(1): 218.
[] [PMID: 34108441]
Zhang Q, Yang J, Bai J, Ren J. Reverse of non-small cell lung cancer drug resistance induced by cancer-associated fibroblasts via a paracrine pathway. Cancer Sci 2018; 109(4): 944-55.
[] [PMID: 29383798]
Zhang YL, Yuan JQ, Wang KF, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: A systematic review and meta-analysis. Oncotarget 2016; 7(48): 78985-93.
[] [PMID: 27738317]
Yi Y, Zeng S, Wang Z, et al. Cancer-associated fibroblasts promote epithelial-mesenchymal transition and EGFR-TKI resistance of non-small cell lung cancers via HGF/IGF-1/ANXA2 signaling. Biochim Biophys Acta Mol Basis Dis 2018; 1864(3): 793-803.
[] [PMID: 29253515]
Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 2014; 4(9): 1046-61.
[] [PMID: 24893891]
Shi Y, Hu X, Zhang S, et al. Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: A phase 2b, multicentre, single-arm, open-label study. Lancet Respir Med 2021; 9(8): 829-39.
[] [PMID: 33780662]
Yang JC, Camidge DR, Yang CT, et al. Safety, efficacy, and pharmacokinetics of Almonertinib (HS-10296) in pretreated patients with EGFR-mutated advanced NSCLC: A multicenter, open-label, phase 1 trial. J Thorac Oncol 2020; 15(12): 1907-18.
[] [PMID: 32916310]
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(9): 725-37.
[] [PMID: 31564718]
Lee Y, Wang Y, James M, Jeong JH, You M. Inhibition of IGF1R signaling abrogates resistance to afatinib (BIBW2992) in EGFR T790M mutant lung cancer cells. Mol Carcinog 2016; 55(5): 991-1001.
[] [PMID: 26052929]
Pan YH, Jiao L, Lin CY, et al. Combined treatment with metformin and gefitinib overcomes primary resistance to EGFR-TKIs with EGFR mutation via targeting IGF-1R signaling pathway. Biologics 2018; 12: 75-86.
[PMID: 30154647]
Han R, Jia Y, Li X, et al. Concurrent use of metformin enhances the efficacy of EGFR-TKIs in patients with advanced EGFR-mutant non-small cell lung cancer-an option for overcoming EGFR-TKI resistance. Transl Lung Cancer Res 2021; 10(3): 1277-91.
[] [PMID: 33889509]
Luo M, Fu LW. Redundant kinase activation and resistance of EGFR-tyrosine kinase inhibitors. Am J Cancer Res 2014; 4(6): 608-28.
[PMID: 25520855]
Zhou J, Wang J, Zeng Y, et al. Implication of epithelial-mesenchymal transition in IGF1R-induced resistance to EGFR-TKIs in advanced non-small cell lung cancer. Oncotarget 2015; 6(42): 44332-45.
[] [PMID: 26554308]
Choi J, Kang M, Nam SH, et al. Bidirectional signaling between TM4SF5 and IGF1R promotes resistance to EGFR kinase inhibitors. Lung Cancer 2015; 90(1): 22-31.
[] [PMID: 26190015]
Hayakawa D, Takahashi F, Mitsuishi Y, et al. Activation of insulin-like growth factor-1 receptor confers acquired resistance to osimertinib in non-small cell lung cancer with EGFR T790M mutation. Thorac Cancer 2020; 11(1): 140-9.
[] [PMID: 31758670]
Guix M, Faber AC, Wang SE, et al. Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest 2008; 118(7): 2609-19.
[] [PMID: 18568074]
Yamaoka T, Ohmori T, Ohba M, et al. Distinct Afatinib Resistance Mechanisms Identified in Lung Adenocarcinoma Harboring an EGFR Mutation. Mol Cancer Res 2017; 15(7): 915-28.
[] [PMID: 28289161]
Wang F, Zhang L, Sai B, et al. BMSC-derived leptin and IGFBP2 promote erlotinib resistance in lung adenocarcinoma cells through IGF-1R activation in hypoxic environment. Cancer Biol Ther 2020; 21(1): 61-71.
[] [PMID: 31559898]
Lu H, Wang L, Gao W, et al. IGFBP2/FAK pathway is causally associated with dasatinib resistance in non-small cell lung cancer cells. Mol Cancer Ther 2013; 12(12): 2864-73.
[] [PMID: 24130049]
Wu SG, Chang TH, Tsai MF, et al. IGFBP7 drives resistance to epidermal growth factor receptor tyrosine kinase inhibition in lung cancer. Cancers (Basel) 2019; 11(1): 11.
[] [PMID: 30609749]
Ma W, Kang Y, Ning L, Tan J, Wang H, Ying Y. Identification of microRNAs involved in gefitinib resistance of non-small-cell lung cancer through the insulin-like growth factor receptor 1 signaling pathway. Exp Ther Med 2017; 14(4): 2853-62.
[] [PMID: 28912847]
Dong S, Qu X, Li W, et al. The long non-coding RNA, GAS5, enhances gefitinib-induced cell death in innate EGFR tyrosine kinase inhibitor-resistant lung adenocarcinoma cells with wide-type EGFR via downregulation of the IGF-1R expression. J Hematol Oncol 2015; 8(1): 43.
[] [PMID: 25925741]
Zhao FY, Han J, Chen XW, et al. miR-223 enhances the sensitivity of non-small cell lung cancer cells to erlotinib by targeting the insulin-like growth factor-1 receptor. Int J Mol Med 2016; 38(1): 183-91.
[] [PMID: 27177336]
Ma W, Feng W, Tan J, et al. miR-497 may enhance the sensitivity of non-small cell lung cancer cells to gefitinib through targeting the insulin-like growth factor-1 receptor. J Thorac Dis 2018; 10(10): 5889-97.
[] [PMID: 30505497]
Wang F, Meng F, Wong SCC, Cho WCS, Yang S, Chan LWC. Combination therapy of gefitinib and miR-30a-5p may overcome acquired drug resistance through regulating the PI3K/AKT pathway in non-small cell lung cancer. Ther Adv Respir Dis 2020; 14: 1753466620915156.
[] [PMID: 32552611]
Liu Z, Yao L, Tan B, Li L, Chen B. Detection of microRNA-200b may predict the inhibitory effect of gefitinib on non-small cell lung cancer and its potential mechanism. Oncol Lett 2016; 12(6): 5349-55.
[] [PMID: 28101246]
Kim JS, Lee SC, Min HY, et al. Activation of insulin-like growth factor receptor signaling mediates resistance to histone deacetylase inhibitors. Cancer Lett 2015; 361(2): 197-206.
[] [PMID: 25721083]
Lee SC, Min HY, Jung HJ, et al. Essential role of insulin-like growth factor 2 in resistance to histone deacetylase inhibitors. Oncogene 2016; 35(42): 5515-26.
[] [PMID: 27086926]
Min HY, Lee SC, Woo JK, et al. Essential role of DNA Methyltransferase 1-mediated transcription of insulin-like growth factor 2 in resistance to histone deacetylase inhibitors. Clin Cancer Res 2017; 23(5): 1299-311.
[] [PMID: 27582487]
Oh SH, Whang YM, Min HY, et al. Histone deacetylase inhibitors enhance the apoptotic activity of insulin-like growth factor binding protein-3 by blocking PKC-induced IGFBP-3 degradation. Int J Cancer 2012; 131(10): 2253-63.
[] [PMID: 22362554]
Jeannot V, Busser B, Vanwonterghem L, et al. Synergistic activity of vorinostat combined with gefitinib but not with sorafenib in mutant KRAS human non-small cell lung cancers and hepatocarcinoma. OncoTargets Ther 2016; 9: 6843-55.
[] [PMID: 27877053]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy