头颈部癌的分子靶向治疗进展_West China Medical Journal

Authors：

刘均 , 唐兴华 ,  赵宇

Corresponding author：

赵宇, Email: liujunluzhou@163.com

Keywords：

头颈部鳞癌; 分子靶向治疗; 进展

DOI：

10.7507/1002-0179.20130299

Video：

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头颈部癌是耳鼻喉常见的肿瘤之一，经首次治疗后局部复发和发生远处转移往往预后较差。分子靶向治疗是以肿瘤细胞过度表达的某些标志性分子为靶点，选择具有针对性的阻断剂来干预受该标志性分子调控、并与肿瘤发生密切相关的信号转导通路，从而抑制肿瘤生长和转移。目前，分子靶向治疗逐渐成为研究热点，有望改善头颈部癌的治疗效果。本文就头颈部癌分子靶向治疗进行综述。

Citation： 刘均,唐兴华,赵宇. 头颈部癌的分子靶向治疗进展. West China Medical Journal, 2013, 28(6): 955-958. doi: 10.7507/1002-0179.20130299 Copy

1.	Hoffmann S, Burchert A, Wunderlich A, et al. Differential effects of cetuximab and AEE 788 on epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) in thyroid Cancer cell lines[J]. Endocrine, 2007, 31(2): 105-113.
2.	Prichard CN, Kim S, Yazici YD, et al. Concurrent cetuximab and bevacizumab therapy in a murine orthotopic model of anaplastic thyroid carcinoma[J]. Laryngoscope, 2007, 117(4): 674-679.
3.	Lothaire P, de Azambuja E, Dequanter D, et al. Molecular markers of head and neck squamous cell carcinoma: promising signs in need of prospective evaluation[J]. Head Neck, 2006, 28(3): 256-269.
4.	O-charoenrat P, Rhys-Evans P, Modjtahedi H, et al. Vascular endothelial growth factor family members are differentially regulated by c-erbB signaling in head and neck squamous carcinoma cells[J]. Clin Exp Metastasis, 2000, 18(2): 155-161.
5.	Vokes EE, Cohen EE, Mauer AM, et al. A phase I study of erlotinib and bevacizumab for recurrent or metastatic squamous cell carcinoma of the head and neck(HNC)[J]. J Clin Oncol, 2005, 23(16S): 5504.
6.	Karamouzis M, Friedland D, Johnson R, et al. Phase II trial of pemetrexed(P)and bevacizumab(B)in patients(pts)with recurrent or metastatic head and neck squamous cell carcinoma(HNSCC):an interim analysis[J]. J Clin Oncol, 2007, 25(18S): 6049.
7.	Gerber HP, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies[J]. Cancer Res, 2005, 65(3): 671-680.
8.	Khan AJ, King BL, Smith BD, et al. Characterization of the HER-2/neu oncogene by immunohistochemical and fluorescence in situ hybridization analysis in oral and oropharyngeal squamous cell carcinoma[J]. Clin Cancer Res, 2002, 8(2): 540-548.
9.	Gillison ML, Glisson BS, O’leary E, et al. Phase II trial of trastuzumab(T), paclitaxel(P)and cisplatin I in metastatic(M)or recurrent I head and neck squamous cell carcinoma(HNSCC): response by tumor EGFR and HER2/neu status[J]. J Clin Oncol, 2006, 24S(18Part 1): 282.
10.	Widakowich C, de Castro G Jr, de Azambuja E, et al. Review: side effects of approved molecular targeted therapies in solid cancers[J]. Oncologist, 2007, 12(12): 1443-1455.
11.	Lanzi C, Cassinelli G, Nicolini V, et al. Targeting RET for thyroid Cancer therapy[J]. Biochem Pharmacol, 2009, 77(3): 297-309.
12.	Diaz-Cano SJ. Motesanib diphosphate in progressive differentiated thyroid Cancer[J]. N Engl J Med, 2008, 359(25): 2727.
13.	Rusnak DW, Lackey K, Affleck K, et al. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo[J]. Mol Cancer Ther, 2001, 1(2): 85-94.
14.	Abidoye OO, Cohen EE, Wong SJ, et al. A phase II study of lapatinib(GW572016)in recurrent/metastatic(R/M)squamous cell carcinoma of the head and neck(SCCHN)[J]. J Clin Oncol, 2006, 24(18S): 5568.
15.	Bourhis J, Harrington K, Rosine D, et al. A phase I,open-label study(EGF100262)of lapatinib plus chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck(SCCHN)[J]. Ann Oncol, 2006, 17(Suppl 9): 180.
16.	Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis[J]. Cancer Res, 2004, 64(19): 7099-7109.
17.	Liu L, Cao Y, Chen C, et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5[J]. Cancer Res, 2006, 66(24): 11851-11858.
18.	Chang YS, Adnane J, Trail PA, et al. Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models[J]. Cancer Chemother Pharmacol, 2007, 59(5): 561-574.
19.	Williamson SK, Moon J, Huang CH, et al. in patients with recurrent and/or metastatic head and neck squamous cell carcinoma(HNSCC): a Southwest Oncology Group ( SWOG ) trial[C]//AY 43-9006, 2006.
20.	Mandal M, Younes M, Swan EA, et al. The Akt inhibitor KP372-1 inhibits proliferation and induces apoptosis and anoikis in squamous cell carcinoma of the head and neck[J]. Oral Oncol, 2006, 42(4): 430-439.
21.	Argiris A, Cohen E, Karrison T, et al. A phase II trial of perifosine,an oral alkylphospholipid, in recurrent or metastatic head and neck Cancer[J]. Cancer Biol Ther, 2006, 5(7): 766-770.
22.	Janmaat ML, Kruyt FA, Rodriguez JA, et al. Response to epidermal growth factor receptor inhibitors in non-small cell lung Cancer cells:limited antiproliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways[J]. Clin Cancer Res, 2003, 9(6): 2316-2326.
23.	Schmelzle T, Hall MN. TOR, a central controller of cell growth[J]. Cell, 2000, 103(2): 253-262.
24.	Aissat N, Le Tourneau C, Ghoul A, et al. Antiproliferative effects of rapamycin as a single agent and in combination with carboplatin and paclitaxel in head and neck Cancer cell lines[J]. Cancer Chemother Pharmacol, 2008, 62(2): 305-313.
25.	Amornphimoltham P, Patel V, Sodhi A, et al. Mammalian target of rapamycin,a molecular target in squamous cell carcinomas of the head and neck[J]. Cancer Res, 2005, 65(21): 9953-9961.
26.	Siesser PM, Hanks SK. The signaling and biological implications of FAK overexpression in Cancer[J]. Clin Cancer Res, 2006, 12(11 Pt 1): 3233-3237.
27.	Johnson FM, Saigal B, Talpaz M, et al. Dasatinib (BMS-354825) tyrosine kinase inhibitor suppresses invasion and induces cell cycle arrest and apoptosis of head and neck squamous cell carcinoma and non-small cell lung Cancer cells[J]. Clin Cancer Res, 2005, 11(19 Pt 1): 6924-6932.
28.	Conticello C, Adamo L, Giuffrida R, et al. Proteasome inhibitors synergize with tumor necrosis factor-related apoptosis-induced ligand to induce anaplastic thyroid carcinoma cell death[J]. J Clin Endocrinol Metab, 2007, 92(5): 1938-1942.
29.	Reiter R, Gais P, Jütting U, et al. Aurora kinase A messenger RNA overexpression is correlated with tumor progression and shortened survival in head and neck squamous cell carcinoma[J]. Clin Cancer Res, 2006, 12(17): 5136-5141.
30.	Schellens JH, Boss D, Witteveen PO, et al. Phase I and pharmacological study of the novel Aurora kinase inhibitor AZD1152[J]. J Clin Oncol, 2006, 24S(18Part 1): 122.
31.	Rubin EH, Shapiro GI, Stein MN, et al. A phase I clinical and pharmacokinetic(Pk)trial of the Aurora kinase(AK)inhibitor MK-0457 in Cancer patients[J]. J Clin Oncol, 2006, 24S(181): 123.
32.	Patel V, Senderowicz AM, Pinto D Jr, et al. Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis[J]. J Clin Invest, 1998, 102(9): 1674-1681.
33.	Marks PA, Rifkind RA, Richon VM, et al. Inhibitors of histone deacetylase are potentially effective anticancer agents[J]. Clin Cancer Res, 2001, 7(4): 759-760.
34.	Zhang Y, Jung M, Dritschilo A, et al. Enhancement of radiation sensitivity of human squamous carcinoma cells by histone deacetylase inhibitors[J]. Radiat Res, 2004, 161(6): 667-674.

1. 　Hoffmann S, Burchert A, Wunderlich A, et al. Differential effects of cetuximab and AEE 788 on epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) in thyroid Cancer cell lines[J]. Endocrine, 2007, 31(2): 105-113.
2. 　Prichard CN, Kim S, Yazici YD, et al. Concurrent cetuximab and bevacizumab therapy in a murine orthotopic model of anaplastic thyroid carcinoma[J]. Laryngoscope, 2007, 117(4): 674-679.
3. 　Lothaire P, de Azambuja E, Dequanter D, et al. Molecular markers of head and neck squamous cell carcinoma: promising signs in need of prospective evaluation[J]. Head Neck, 2006, 28(3): 256-269.
4. 　O-charoenrat P, Rhys-Evans P, Modjtahedi H, et al. Vascular endothelial growth factor family members are differentially regulated by c-erbB signaling in head and neck squamous carcinoma cells[J]. Clin Exp Metastasis, 2000, 18(2): 155-161.
5. 　Vokes EE, Cohen EE, Mauer AM, et al. A phase I study of erlotinib and bevacizumab for recurrent or metastatic squamous cell carcinoma of the head and neck(HNC)[J]. J Clin Oncol, 2005, 23(16S): 5504.
6. 　Karamouzis M, Friedland D, Johnson R, et al. Phase II trial of pemetrexed(P)and bevacizumab(B)in patients(pts)with recurrent or metastatic head and neck squamous cell carcinoma(HNSCC):an interim analysis[J]. J Clin Oncol, 2007, 25(18S): 6049.
7. 　Gerber HP, Ferrara N. Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies[J]. Cancer Res, 2005, 65(3): 671-680.
8. 　Khan AJ, King BL, Smith BD, et al. Characterization of the HER-2/neu oncogene by immunohistochemical and fluorescence in situ hybridization analysis in oral and oropharyngeal squamous cell carcinoma[J]. Clin Cancer Res, 2002, 8(2): 540-548.
9. 　Gillison ML, Glisson BS, O’leary E, et al. Phase II trial of trastuzumab(T), paclitaxel(P)and cisplatin I in metastatic(M)or recurrent I head and neck squamous cell carcinoma(HNSCC): response by tumor EGFR and HER2/neu status[J]. J Clin Oncol, 2006, 24S(18Part 1): 282.
10. 　Widakowich C, de Castro G Jr, de Azambuja E, et al. Review: side effects of approved molecular targeted therapies in solid cancers[J]. Oncologist, 2007, 12(12): 1443-1455.
11. 　Lanzi C, Cassinelli G, Nicolini V, et al. Targeting RET for thyroid Cancer therapy[J]. Biochem Pharmacol, 2009, 77(3): 297-309.
12. 　Diaz-Cano SJ. Motesanib diphosphate in progressive differentiated thyroid Cancer[J]. N Engl J Med, 2008, 359(25): 2727.
13. 　Rusnak DW, Lackey K, Affleck K, et al. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumor-derived cell lines in vitro and in vivo[J]. Mol Cancer Ther, 2001, 1(2): 85-94.
14. 　Abidoye OO, Cohen EE, Wong SJ, et al. A phase II study of lapatinib(GW572016)in recurrent/metastatic(R/M)squamous cell carcinoma of the head and neck(SCCHN)[J]. J Clin Oncol, 2006, 24(18S): 5568.
15. 　Bourhis J, Harrington K, Rosine D, et al. A phase I,open-label study(EGF100262)of lapatinib plus chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck(SCCHN)[J]. Ann Oncol, 2006, 17(Suppl 9): 180.
16. 　Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis[J]. Cancer Res, 2004, 64(19): 7099-7109.
17. 　Liu L, Cao Y, Chen C, et al. Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5[J]. Cancer Res, 2006, 66(24): 11851-11858.
18. 　Chang YS, Adnane J, Trail PA, et al. Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models[J]. Cancer Chemother Pharmacol, 2007, 59(5): 561-574.
19. 　Williamson SK, Moon J, Huang CH, et al. in patients with recurrent and/or metastatic head and neck squamous cell carcinoma(HNSCC): a Southwest Oncology Group ( SWOG ) trial[C]//AY 43-9006, 2006.
20. 　Mandal M, Younes M, Swan EA, et al. The Akt inhibitor KP372-1 inhibits proliferation and induces apoptosis and anoikis in squamous cell carcinoma of the head and neck[J]. Oral Oncol, 2006, 42(4): 430-439.
21. 　Argiris A, Cohen E, Karrison T, et al. A phase II trial of perifosine,an oral alkylphospholipid, in recurrent or metastatic head and neck Cancer[J]. Cancer Biol Ther, 2006, 5(7): 766-770.
22. 　Janmaat ML, Kruyt FA, Rodriguez JA, et al. Response to epidermal growth factor receptor inhibitors in non-small cell lung Cancer cells:limited antiproliferative effects and absence of apoptosis associated with persistent activity of extracellular signal-regulated kinase or Akt kinase pathways[J]. Clin Cancer Res, 2003, 9(6): 2316-2326.
23. 　Schmelzle T, Hall MN. TOR, a central controller of cell growth[J]. Cell, 2000, 103(2): 253-262.
24. 　Aissat N, Le Tourneau C, Ghoul A, et al. Antiproliferative effects of rapamycin as a single agent and in combination with carboplatin and paclitaxel in head and neck Cancer cell lines[J]. Cancer Chemother Pharmacol, 2008, 62(2): 305-313.
25. 　Amornphimoltham P, Patel V, Sodhi A, et al. Mammalian target of rapamycin,a molecular target in squamous cell carcinomas of the head and neck[J]. Cancer Res, 2005, 65(21): 9953-9961.
26. 　Siesser PM, Hanks SK. The signaling and biological implications of FAK overexpression in Cancer[J]. Clin Cancer Res, 2006, 12(11 Pt 1): 3233-3237.
27. 　Johnson FM, Saigal B, Talpaz M, et al. Dasatinib (BMS-354825) tyrosine kinase inhibitor suppresses invasion and induces cell cycle arrest and apoptosis of head and neck squamous cell carcinoma and non-small cell lung Cancer cells[J]. Clin Cancer Res, 2005, 11(19 Pt 1): 6924-6932.
28. 　Conticello C, Adamo L, Giuffrida R, et al. Proteasome inhibitors synergize with tumor necrosis factor-related apoptosis-induced ligand to induce anaplastic thyroid carcinoma cell death[J]. J Clin Endocrinol Metab, 2007, 92(5): 1938-1942.
29. 　Reiter R, Gais P, Jütting U, et al. Aurora kinase A messenger RNA overexpression is correlated with tumor progression and shortened survival in head and neck squamous cell carcinoma[J]. Clin Cancer Res, 2006, 12(17): 5136-5141.
30. 　Schellens JH, Boss D, Witteveen PO, et al. Phase I and pharmacological study of the novel Aurora kinase inhibitor AZD1152[J]. J Clin Oncol, 2006, 24S(18Part 1): 122.
31. 　Rubin EH, Shapiro GI, Stein MN, et al. A phase I clinical and pharmacokinetic(Pk)trial of the Aurora kinase(AK)inhibitor MK-0457 in Cancer patients[J]. J Clin Oncol, 2006, 24S(181): 123.
32. 　Patel V, Senderowicz AM, Pinto D Jr, et al. Flavopiridol, a novel cyclin-dependent kinase inhibitor, suppresses the growth of head and neck squamous cell carcinomas by inducing apoptosis[J]. J Clin Invest, 1998, 102(9): 1674-1681.
33. 　Marks PA, Rifkind RA, Richon VM, et al. Inhibitors of histone deacetylase are potentially effective anticancer agents[J]. Clin Cancer Res, 2001, 7(4): 759-760.
34. 　Zhang Y, Jung M, Dritschilo A, et al. Enhancement of radiation sensitivity of human squamous carcinoma cells by histone deacetylase inhibitors[J]. Radiat Res, 2004, 161(6): 667-674.

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头颈部癌的分子靶向治疗进展

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