头颈鳞癌表皮生长因子受体靶向治疗抵抗机制的研究进展

宋琦; 李晓明

doi:10.13201/j.issn.1001-1781.2015.02.027

头颈鳞癌表皮生长因子受体靶向治疗抵抗机制的研究进展

宋琦¹,
李晓明^2, ,

- 1 解放军医学院(北京, 100853);
- 2 白求恩国际和平医院耳鼻咽喉头颈外科

详细信息

通讯作者: 李晓明,E-mail:xmlmo@126.com

中图分类号: R739.91

收稿日期: 2014-07-25

Research progress of squamous cell carcinoma of head and neck EGFR targeted therapy resistance mechanisms

SONG Qi¹,
LI Xiaoming^2, ,

More Information

Corresponding author: LI Xiaoming, E-mail: xmlmo@126.com

Received Date: 25 July 2014

摘要

- 头颈部鳞状细胞癌 /
- 表皮生长因子受体
Abstract: Overexpression of the epidermal growth factor receptor(EGFR)is a common characteristic of head and neck squamous cell carcinomas(HNSCC),and initiates important signal transduction pathways in carcinogenesis.Now the EGFR is a validated target for cancer therapies in HNSCC.However,the effect of EGFR-targeted therapies is only modest because of primary and/or acquired resistance.Therefore,an improved understanding of the molecular mechanisms of resistance to EGFR inhibitors may establish new treatment options to overcome resistance.In this review,the molecular mechanisms of resistance and the strategies to overcome it were summarized.
- head and neck squamous cell carcinoma /
- epidermal growth factor receptor

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参考文献(52)

[1]	ANG K K, BERKEY B A, TU X, et al. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma[J]. Cancer Res, 2002,62:7350-7356.
[2]	NICOLA N, MARIA P, ALESSIA L, et al. Mechanisms of action of EGFR inhibitors[M]//PATRICK J, eds. EGFR Inhibitors in Cancer Treatment. Britain:Future Medicine Ltd, 2012:6-17.
[3]	VERMORKEN J B, HERBST R S, LEON X, et al. Overview of the efficacy of cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck in patients who previously failed platinum-based therapies[J]. Cancer, 2008,112:2710-2719.
[4]	DITTMANN K, MAYER C, RODEMANN H P. Nuclear EGFR as novel therapeutic target:insights into nuclear translocation and function[J]. Strahlenther Onkol, 2010,186:1-6.
[5]	HATAKEYAMA H, CHENG H, WIRTH P, et al. Regulation of heparin-binding EGF-like growth factor by miR-212 and acquired cetuximab-resistance in head and neck squamous cell carcinoma[J]. PloS One, 2010,5:e12702.
[6]	JIJON H B, BURET A, HIROTA C L, et al. The EGF receptor and HER2 participate in TNF-α-dependent MAPK activation and IL-8 secretion in intestinal epithelial cells[J]. Mediators Inflamm, 2012,2012:207398-207398.
[7]	TINHOFER I, KLINGHAMMER K, WEICHERT W, et al. Expression of amphiregulin and EGFRvIII affect outcome of patients with squamous cell carcinoma of the head and neck receiving cetuximab-docetaxel treatment[J]. Clin Cancer Res, 2011, 17:5197-5204.
[8]	LAURENT-PUIG P, LIEVRE A, BLONS H. Mutations and response to epidermal growth factor receptor inhibitors[J]. Clin Cancer Res, 2009, 15:1133-1139.
[9]	WILLMORE-PAYNE C, HOLDEN J A, LAYFI-ELD L J. Detection of EGFR-and HER2-activating mutations in squamous cell carcinoma involving the head and neck[M]. Mod Pathol, 2006, 19:634-640.
[10]	HUANG S F, CHUANG W Y, CHEN I H, et al. EGFR protein overexpression and mutation in areca quid-associated oral cavity squamous cell carcinoma in Taiwan[J]. Head Neck, 2009, 31:1068-1077.
[11]	NA I I, KANG H J, CHO S Y, et al. EGFR mutations and human papillomavirus in squamous cell carcinoma of tongue and tonsil[J]. European J Cancer, 2007, 43:520-526.
[12]	WHEELER S E, SUZUKI S, THOMAS S M, et al. Epidermal growth factor receptor variant III mediates head and neck cancer cell invasion via STAT3 activation[J]. Oncogene, 2010, 29:5135-5145.
[13]	HAMA T, YUZA Y, SAITO Y, et al. Prognostic significance of epidermal growth factor receptor phosphorylation and mutation in head and neck squamous cell carcinoma[J]. Oncologist, 2009, 14:900-908.
[14]	PECTASIDES E, FOUNTZILAS G, KOUNTOURAKIS P, et al. Evaluation of the incidence and prognostic value of mutant epidermal growth factor receptor (EGFRvIII) protein expression in head and neck squamous cell carcinomas (HNSCC) using AQUA[J]. ASCO Meeting Abstracts, 2010, 28:5538-14.
[15]	MCINTYRE J B, BOSE P, KLIMOWICZ A C, et al. Specific and sensitive hydrolysis probe-based real-time PCR detection of epidermal growth factor receptor variant III in oral squamous cell carcinoma[J]. PloS One, 2012, 7:e31723-31723.
[16]	LICCARDI G, HARTLEY J A, HOCHHAUSER D. EGFR nuclear translocation modulates DNA repair following cisplatin and ionizing radiation treatment[J]. Cancer Res, 2011, 71:1103-1114.
[17]	LI C, IIDA M, DUNN E F, et al. Nuclear EGFR contributes to acquired resistance to cetuximab[J]. Oncogene, 2009, 28:3801-3813.
[18]	MORRIS L G, TAYLOR B S, BIVONA T G, et al. Genomic dissection of the epidermal growth factor receptor (EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers[J]. Proc Nati Acad, 2011, 108:19024-19029.
[19]	FUJII S, URYU H, AKASHI K, et al. Clinical significance of KRAS gene mutation and epidermal growth factor receptor expression in Japanese patients with squamous cell carcinoma of the larynx, oropharynx and hypopharynx[J]. Int J Clin Oncol, 2013, 18:454-463.
[20]	VAN DAMME N, DERON P, VAN ROY N, et al. Epidermal growth factor receptor and K-RAS status in two cohorts of squamous cell carcinomas[J]. BMC Cancer, 2010, 10:189-189.
[21]	YARBROUGH W G, SHORES C, WITSELL D L, et al. ras mutations and expression in head and neck squamous cell carcinomas[J].Laryngoscope, 1994, 104:1337-1347.
[22]	RAMPIAS T, GIAGINI A, MATSUZAKI H, et al. Genetic alterations in HRAS gene in relation to outcome and response to cetuximab in head and neck squamous cell carcinoma[J]. ASCO Meeting Abstracts, 2012, 30:5574.
[23]	RAMPIAS T, GIAGINI A, FLOROU K, et al. H-RAS and PIK3CA mutations and response to cetuximab in head and neck squamous cell carcinoma (HNSCC)[J]. ASCO Meeting Abstracts, 2011, 29:5513.
[24]	ARKELL R S, DICKINSON R J, SQUIRES M, et al. DUSP6/MKP-3 inactivates ERK1/2 but fails to bind and inactivate ERK5[J]. Cell Signal, 2008, 20:836-843.
[25]	QIU W, SCHONLEBEN F, LI X, et al. PIK3CA mutations in head and neck squamous cell carcinoma[J]. Clin Cancer Res, 2006,12:1441-1446.
[26]	REBUCCI M, PEIXOTO P, DEWITTE A, et al. Mechanisms underlying resistance to cetuximab in the HNSCC cell line:role of AKT inhibition in bypassing this resistance[J]. Int J Oncol, 2011, 38:189-200.
[27]	YAMATODANI T, EKBLAD L, KJELLEN E, et al. Epidermal growth factor receptor status and persistent activation of Akt and p44/42 MAPK pathways correlate with the effect of cetuximab in head and neck and colon cancer cell lines[J]. J Cancer Res, 2009, 135:395-402.
[28]	LI C, IIDA M, DUNN E F, et al. Dasatinib blocks cetuximab- and radiation-induced nuclear translocation of the epidermal growth factor receptor in head and neck squamous cell carcinoma[J]. Radiother Oncol, 2010, 97:330-337.
[29]	BONNER J A, YANG E S, TRUMMELL H Q, et al. Inhibition of STAT-3 results in greater cetuximab sensitivity in head and neck squamous cell carcinoma[J]. Radiotherapy and oncology, 2011, 99:339-343.
[30]	ONISHI A, CHEN Q, HUMTSOE J O, et al. STAT3 signaling is induced by intercellular adhesion in squamous cell carcinoma cells[J]. Experimental Cell Res, 2008, 314:377-386.
[31]	QUESNELLE K M, GRANDIS J R. Dual kinase inhibition of EGFR and HER2 overcomes resistance to cetuximab in a novel in vivo model of acquired cetuximab resistance[J]. Clin Cancer Res,2011, 17:5935-5944.
[32]	YONESAKA K, ZEJNULLAHU K, OKAMOTO I, et al. Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab[J]. Science Translational Medicine, 2011, 3:99ra86.
[33]	POLLAK M. Insulin and insulin-like growth factor signalling in neoplasia[J]. Nat Rev Cancer, 2008, 8:915-928.
[34]	BARNES C J, OHSHIRO K, RAYALA S K, et al. Insulin-like growth factor receptor as a therapeutic target in head and neck cancer[J]. Clin Cancer Res, 2007, 13:4291-4299.
[35]	SIERRA J R, TSAO M S. c-MET as a potential therapeutic target and biomarker in cancer[J]. Therapeutic Advances Med Oncol, 2011, 3(1 Suppl):S21-35.
[36]	KNOWLES L M, STABILE L P, EGLOFF A M, et al. HGF and c-Met participate in paracrine tumorigenic pathways in head and neck squamous cell cancer[J]. Clin Cancer Res, 2009, 15:3740-3750.
[37]	SEIWERT T Y, JAGADEESWARAN R, FAORO L, et al. The MET receptor tyrosine kinase is a potential novel therapeutic target for head and neck squamous cell carcinoma[J]. Cancer Res, 2009, 69:3021-3031.
[38]	CHAU N G, PEREZ-ORDONEZ B, ZHANG K, et al. The association between EGFR variant III, HPV, p16, c-MET, EGFR gene copy number and response to EGFR inhibitors in patients with recurrent or metastatic squamous cell carcinoma of the head and neck[J]. Head Neck Oncol, 2011, 3:11.
[39]	KELLY K R, ECSEDY J, MAHALINGAM D, et al. Targeting aurora kinases in cancer treatment[J]. Current Drug Targets, 2011, 12:2067-2078.
[40]	HOELLEIN A, PICKHARD A, VON KEITZ F, et al. Aurora kinase inhibition overcomes cetuximab resistance in squamous cell cancer of the head and neck[J]. Oncotarget, 2011, 2:599-609.
[41]	HUNG L Y, TSENG J T, LEE Y C, et al. Nuclear epidermal growth factor receptor (EGFR) interacts with signal transducer and activator of transcription 5(STAT5) in activating Aurora-A gene expression[J]. Nucleic Acids Res, 2008, 36:4337-51.
[42]	FREDERICK B A, HELFRICH B A, COLDREN C D, et al. Epithelial to mesenchymal transition predicts gefitinib resistance in cell lines of head and neck squamous cell carcinoma and non-small cell lung carcinoma[J]. Molecular Cancer Therapeutics, 2007, 6:1683-1691.
[43]	HOLZ C, NIEHR F, BOYKO M, et al. Epithelial-mesenchymal-transition induced by EGFR activation interferes with cell migration and response to irradiation and cetuximab in head and neck cancer cells[J]. Radiother Oncol, 2011, 101:158-164.
[44]	WOUTERS A, BOECKX C, VERMORKEN J B, et al. The intriguing interplay between therapies targeting the epidermal growth factor receptor, the hypoxic microenvironment and hypoxia-inducible factors[J]. Current Pharmaceutical Design, 2013, 19:907-917.
[45]	WANG X, SCHNEIDER A. HIF-2alpha-mediated activation of the epidermal growth factor receptor potentiates head and neck cancer cell migration in response to hypoxia[J]. Carcinogenesis, 2010, 31:1202-1210.
[46]	HOOGSTEEN I J, MARRES H A, VAN DEN HOOGEN F J, et al. Expression of EGFR under tumor hypoxia:identification of a subpopulation of tumor cells responsible for aggressiveness and treatment resistance[J]. Int J Rad Oncol, 2012, 84:807-814.
[47]	LU H, LIANG K, LU Y, et al. The anti-EGFR antibody cetuximab sensitizes human head and neck squamous cell carcinoma cells to radiation in part through inhibiting radiation-induced upregulation of HIF-1alpha[J]. Cancer Lett, 2012, 322:78-85.
[48]	SCHMITZ S, KAMINSKY-FORRETT M C, HENRY S, et al. Phase II study of figitumumab in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck:clinical activity and molecular response (GORTEC 2008-02)[J]. Ann Oncol, 2012, 23:2153-2161.
[49]	CHUNG C H, POHLMANN P R, ROTHENBERG M L, et al. Insulin-like growth factor-1 receptor inhibitor, AMG-479, in cetuximab-refractory head and neck squamous cell carcinoma[J]. Head Neck, 2011, 33:1804-1808.
[50]	BROOKS H D, GLISSON B S, BEKELE B N, et al. Phase 2 study of dasatinib in the treatment of head and neck squamous cell carcinoma[J]. Cancer, 2011, 117:2112-2119.
[51]	FURY M G, BAXI S, SHEN R, et al. Phase II study of saracatinib (AZD0530) for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)[J]. Anticancer Res, 2011, 31:249-253.
[52]	DE SOUZA J A, DAVIS D W, ZHANG Y, et al. A phase II study of lapatinib in recurrent/metastatic squamous cell carcinoma of the head and neck[J]. Clin Cancer Res, 2012, 18:2336-2343.