Abnormal activation of insulin-like growth factor-I receptor in hepatocellular carcinoma and potential of IGF-IR targeted therapy
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摘要:
肝细胞恶性转化和癌变过程中,胰岛素样生长因子-I受体(IGF-IR)异常活化。IGF-IR过表达既可作为肝癌早期诊断的标志,又可作为肝癌靶向治疗的新靶点,且具有应用前景。本文对IGF-IR信号通路异常激活及分子靶向治疗肝癌等的研究进展作了综述。
Abstract:Abnormal activation of the insulin-like growth factor-I receptor (IGF-IR) occurs during malignant transformation of hepatocytes and during hepatocarcinogenesis.IGF-IR overexpression has been proposed as a diagnostic biomarker for early-stage hepatocellular carcinoma (HCC) as well as a novel target for HCC therapy.This review summarizes the recent research of the IGF-IR signaling pathway's abnormal activation in HCC and the results of molecular targeting studies.
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Key words:
- liver neoplasms /
- receptor /
- IGF type I /
- antibodies
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[1]Tovar V, Alsinet C, Villanueva A, et al.IGF activation in a molec-ular subclass of hepato-cellular carcinoma and pre-clinical effi-cacy of IGF-1R blockage[J].J Hepatol, 2010, 52 (4) :550-559. [2] Pollak M.Insulin and insulin-like growth factor signalling in neo-plasia[J].Nat Rev Cancer, 2008, 8 (12) :915-928. [3] Rosenzweig SA, Atreya HS. Defining the pathway to insulin-like growth factor system targeting in cancer[J]. Biochem Pharmacol, 2010, 80 (8) : 1115-1124. [4]Adachi Y, Yamamoto H, Ohashi H, et al.A candidate targetingmolecule of insulin-like growth factor-I receptor for gastrointesti-nal cancers[J].World J Gastroenterol, 2010, 16 (46) :5779-5789. [5]Naj AC, Kao WH, O'Connell JR, et al.Sequence variation inIGF1R is associated with differences in insulin levels in nondiabeticOld Order Amish[J].Diabetes Metab Res Rev, 2009, 25 (8) :773-779. [6]Escobar S, Fuentes EN, Poblete E, et al.Molecular cloning of IGF-1 and IGF-1 receptor and their expression pattern in the Chileanflounder (Paralichthys adspersus) [J].Comp Biochem Physiol B Bio-chem Mol Biol, 2011, 159 (3) :140-147. [7] Qian J, Yao DF, Dong ZZ, et al. Characteristics of hepatic IGF-Ⅱexpression and monitored levels of circulating IGF-ⅡmRNA in metastasis of hepatocellular carcinoma[J]. Am J Clin Pathol, 2010, 134 (5) : 799-806. [8] Valenciano A, Henríquez-Hernández LA, Moreno M, et al. Role of IGF-1 receptor in radiation response [J]. Transl Oncol, 2012, 5 (1) : 1-9. [9]Qiu LW, Yao DF, Zong L, et al.Abnormal expression of insulin-like growth factor-II and its dynamic quantitative analysis at differ-ent stages of hepatocellular carcinoma development[J].Hepatobili-ary Pancreat Dis Int, 2008, 7 (4) :406-411. [10] Xue M, Cao X, Zhong Y, et al. Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors in cancer therapy: advances and perspectives [J]. Curr Pharm Des, 2012, 18 (20) : 2901-2913. [11] Zhao HF. p53 regulation of the IGF-1/AKT/mTOR pathways and the endosomal compartment [J]. Cold Spring Harb Perspect Biol, 2010, 2 (2) : a001057. [12]Aiello A, Pandini G, Sarfstein R, et al.HMGA1 protein is a posi-tive regulator of the insulin-like growth factor-I receptor gene[J].Eur J Cancer, 2010, 46 (10) :1919-1926. [13] Ubagai T, Kikuchi T, Fukusato T, et al. Aflatoxin B1 modulates the insulin-like growth factor-2 dependent signaling axis [J]. Toxicol In Vitro, 2010, 24 (3) : 783-789. [14]Caliebe J, Broekman S, Boogaard M, et al.IGF1, IGF1R andSHOX mutation analysis in short children born small for gestationalage and short children with normal birth size (idiopathic short sta-ture) [J].Horm Res Paediatr, 2012, 77 (4) :250-260. [15] Kawashima Y, Higaki K, Fukushima T, et al. Novel missense mutation in the IGF-I receptor L2 domain results in intrauterine and postnatal growth retardation [J]. Clin Endocrinol (Oxf) , 2012, 77 (2) : 1365-2265. [16] Siwicky MD, Petrik JJ, Moorehead RA. The function of IGF-IR in NNK-mediated lung tumorigenesis [J]. Lung Cancer, 2011, 71 (1) : 11-18. [17]Breuhahn K, Schirmacher P.Reactivation of the insulin-likegrowth factor-signaling pathway in human hepatocellular carci-noma[J].World J Gastroenterol, 2008, 14 (11) :1690-1698. [18]Graeser R, Vrignaud P, Esser N, et al.Generation of a condition-ally transformed murine embryonic fibroblast cell line using doxy-cycline-dependent IGF-1R overexpression[J].J BiomolScreen, 2012, 17 (3) :339-349. [19]Kim JG, Kang MJ, Yoon YK, et al.Heterodimerization of glyco-sylated insulin-like growth factor-1 receptors and insulin recep-tors in cancer cells sensitive to anti-IGF1R antibody[J].PLoSOne, 2012, 7 (3) :e33322. [20]McKinley ET, Bugaj JE, Zhao P, et al.18FDG-PET predictspharmacodynamic response to OSI-906, a Dual IGF-1R/IR in-hibitor, inpreclinical mouse models of lung cancer[J].ClinCancer Res, 2011, 17 (10) :3332-3340. [21]Zhao H, Desai V, Wang J, et al.Epithelial-mesenchyma l tran-sition predicts sensitivity to the dual IGF-1R/IR inhibitor OSI-906 in hepatocellular carcinoma cell lines[J].Mol Cancer Ther, 2012, 11 (2) :503-513. [22]Hadad SM, Appleyard V, Thompson AM.Therapeutic metformin/AMPK activation promotes the angiogenic phenotype in the ERal-pha negative MDA-MB-435 breast cancer model[J].BreastCancer Res Treat, 2009, 114 (2) :391. [23] Bao XH, Takaoka M, Hao HF, et al. Esophageal cancer exhibits resistance to a novel IGF-1R inhibitor NVP-AEW541 with maintained RAS-MAPK activity [J]. Anticancer Res, 2012, 32 (7) : 2827-2834. [24]Zhou H, Rao J, Lin J, et al.The insulin-like growth factor-I re-ceptor kinase inhibitor NVP-ADW742 sensitizes medullo-blastoma-to the effects of chemotherapy[J].Oncol Rep, 2011, 25 (6) :1565-1571. [25]Yao WF, Liu JW, Sheng GL, et al.Blockade of IGF-IR exertsanticancer effects in hepatocellular carcinoma[J].Mol Med Re-port, 2011, 4 (4) :719-722. [26] Yang L, Li J, Ran L, et al. Phosphorylated insulin-like growth factor 1 receptor is implicated in resistance to the cytostatic effect of gefitinib in colorectal cancer cells [J]. J Gastrointest Surg, 2011, 15 (6) : 942-957. [27]Tanaka S, Arii S.Molecular targeted therapy for hepatocellularcarcinoma in the current and potential next strategies[J].J Gas-troenterol, 2011, 46 (3) :289-296. [28]Liu L, Zhu XD, Wang WQ, et al.Activation of beta-catenin byhypoxia in hepatocellular carcinoma contributes to enhanced meta-static potential and poor prognosis[J].Clin Cancer Res, 2010, 16 (10) :2740-2750. [29]Wu J, Zhu AX.Targeting insulin-like growth factor axis in hepato-cellular carcinoma[J].J Hematol Oncol, 2011, 4:30. [30]Atzori F, Tabernero J, Cervantes A, et al.Phase I pharmacokineticand pharmacodynamic study of dalotuzumab (MK-0646) , an anti-insulin-like growth factor-1 receptor monoclonal antibody, in pa-tients with advanced solid tumors[J].Clin Cancer Res, 2011, 17 (19) :6304-6312. [31] McKian KP, Haluska P. Cixutumumab [J]. Expert Opin Investig Drugs, 2009, 18 (7) : 1025-1033. [32]Attias-Geva Z, Bentov I, Ludwig DL, et al.Insulin-likegrowth factor-I receptor (IGF-IR) targeting with monoclonalantibody cixutumumab (IMC-A12) inhibits IGF-I action in en-dometrial cancer cells[J].Eur J Cancer, 2011, 47 (11) :1717-1726. [33]Tovar V, Alsinet C, Villanueva A, et al.IGF activation in a mo-lecular subclass of hepato-cellular carcinoma and pre-clinicalefficacy of IGF-IR blockage[J].J Hepatol, 2010, 52 (4) :550-559. [34] Karp DD, Paz-Ares LG, Novello S, et al. Phase II study of the anti-insulin-like growth factor type I receptor antibody CP-751871 in combination with paclitaxel and carboplatin in previously untreated, locally advanced, or metastatic non small cell lung cancer [J]. J Clin Oncol, 2009, 27 (15) : 2516-2522. [35]Hewish M, Chau I, Cunningham D.Insulin-like growth factor 1receptor targeted therapeutics:novel compounds and novel treat-ment strategies for cancer medicine[J].Recent Pat AnticancerDrug Discov, 2009, 4 (1) :54-72. [36]Scartozzi M, Bianconi M, Maccaroni E, et al.State of the art andfuture perspectives for the use of insulin-like growth factor recep-tor 1 (IGF-1R) targeted treatment strategies in solid tumors[J].Discov Med, 2011, 11 (57) :144-153. [37]Desbois-Mouthon C, Baron A, Fartoux L, et al.Insulin-likegrowth factor-1 receptor inhibition induces a resistance mecha-nism via the epidermal growth factor receptor/HER3/AKT signa-ling pathway:rational basis for cotargeting insulin-like growthfactor-1 receptor and epidermal growth factor receptor in hepato-cellular carcinoma[J].Clin Cancer Res, 2009, 15 (17) :5445-5456. [38] Molife LR, Fong PC, Paccagnella L, et al. The insulin-like growth factor-I receptor inhibitor figitumumab (CP-751, 871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose-escalation, open-label study [J]. Br J Cancer, 2010, 103 (3) : 332-339. [39] Kurzrock R, Patnaik A, Aisner J, et al. A phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors [J]. Clin Cancer Res, 2010, 16 (8) : 2458-2465. [40]Mendivil A, Zhou C, Cantrell LA, et al.AMG 479, a novel IGF-IR antibody, inhibits endometrial cancer cell proliferationthrough disruption of the PI3K/Akt and MAPK pathways[J].Re-prod Sci, 2011, 18 (9) :832-841. [41]Bai S, Nasser MW, Wang B, et al.MicroRNA-122 inhibits tu-morigenic properties of hepatocellular carcinoma cells and sensitizesthese cells to sorafenib[J].J Biol Chem, 2009, 284 (46) :32015-32027. [42]Runnels HA, Arbuckle JA, Bailey KS, et al.Human monoclonalantibodies to the insulin-like growth factor 1 receptor inhibit re-ceptor activation and tumor growth in preclinical studies[J].AdvTher, 2010, 27 (7) :458-475.
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