孙昭;白春梅;

• 1:中国医学科学院北京协和医学院北京协和医院肿瘤内科

摘要(Abstract)：

<正>结直肠癌为临床常见恶性肿瘤之一,在西方国家位列肿瘤死亡率的第2位,在我国位列第4位。分子靶向治疗是结直肠癌除外科手术、放疗和化疗之外的一种新的治疗手段,针对表皮生长因子受体

关键词(KeyWords)： 结直肠癌;表皮生长因子受体;单克隆抗体;生物学标志物

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 孙昭;白春梅;

Email:

DOI:

参考文献(References)：

• [1]Siena S,Sartore-Bianchi A,Di Nicolantonio F,et al.Bio-markers predicting clinical outcome of epidermal growth fac-tor receptor-targeted therapy in metastatic colorectal cancer[J].J Natl Cancer Inst,2009,101:1308-1324.
• [2]Cunningham D,Humblet Y,Siena S,et al.Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-re-fractory metastatic colorectal cancer[J].N Engl J Med,2004,351:337-345.
• [3]Van Cutsem E,Siena S,Humblet Y,et al.An open-label,single-arm study assessing safety and efficacy of panitumum-ab in patients with metastatic colorectal cancer refractory to standard chemotherapy[J].Ann Oncol,2008,19:92-98.
• [4]McCubrey JA,Steelman LS,Chappell WH,et al.Roles of the Raf/MEK/ERKpathway in cell growth,malignant trans-formation and drug resistance[J].Biochim Biophys Acta,2007,1773:1263-1284.
• [5]McCubrey JA,Steelman LS,Abrams SL,et al.Roles of the RAF/MEK/ERK and PI3K/PTEN/AKTpathways in malig-nant transformation and drug resistance[J].Adv Enzyme Regul,2006,46:249-279.
• [6]Lièvre A,Bachet JB,Boige V,et al.KRAS mutations as an independent prognostic factor in patients with advanced colo-rectal cancer treated with cetuximab[J].J Clin Oncol,2008,26:374-379.
• [7]Jonker DJ,O Callaghan CJ,Karapetis CS,et al.Cetuximab for the treatment of colorectal cancer[J].N Engl J Med,2007,357:2040-2048.
• [8]Karapetis CS,Khambata-Ford S,Jonker DJ,et al.K-ras mutations and benefit from cetuximab in advanced colorectal cancer[J].N Engl J Med,2008,359:1757-1765.
• [9]Bokemeyer C,Bondarenko I,Hartmann JT,et al.K-RAS status and efficacy of first-line treatment of patients with me-tastatic colorectal cancer with FOLFOX with or without cetuximab:the OPUS experience(abstract)[J].J Clin Oncol,2008,26:178s.
• [10]Van Cutsem E,K hne CH,Hitre E,et al.Cetuximab and chemotherapy as initial treatment for metastatic colorectalcancer[J].N Engl J Med,2009,360:1408-1417.
• [11]蒲兴祥,邓艳红,徐菲,等.KRAS突变对晚期结直肠癌C225联合化疗疗效的影响[J].中华胃肠外科杂志,2008,12:594-597.
• [12]庄荣源,刘天舒,周宇红,等.西妥昔单抗联合化疗治疗转移性结直肠癌疗效与KRAS状态的关系[J].中国癌症杂志,2009,19:943-946.
• [13]De Roock W,Piessevaux H,De Schutter J,et al.KRAS wild-type state predicts survival and is associated to early ra-diological response in metastatic colorectal cancer treated with cetuximab[J].Ann Oncol,2008,19:508-515.
• [14]Di Nicolantonio F,Martini M,Molinari F,et al.A wild-type BRAFis required forresponse to panitumumab orcetux-imab in metastatic colorectal cancer[J].J Clin Oncol,2008,26:5705-5712.
• [15]Sartore-Bianchi A,Martini M,Molinari F,et al.PIK3CA mutations in colorectal cancer are associated with clinical re-sistance to EGFR-targeted monoclonal antibodies[J].Canc-er Res,2009,69:1851-1857.
• [16]Perrone F,Lampis A,Orsenigo M,et al.PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients[J].Ann Oncol,2009,20:84-90.
• [17]Razis E,Briasoulis E,Vrettou E,et al.Potential value of PTEN in predicting cetuximab response in colorectal cancer:an exploratory study[J].BMC Cancer,2008,8:234.
• [18]Shia J,Klimstra DS,Li AR,et al.Epidermal growth factor receptor expression and gene amplification in colorectal car-cinoma:an immunohistochemical and chromogenic in situ hybridization study[J].Mod Pathol,2005,18:1350-1356.
• [19]Scartozzi M,Bearzi I,Berardi R,et al.Epidermal growth factor receptor(EGFR)status in primary colorectal tumorsdoes notcorrelate with EGFR expression in related metastatic sites:implications for treatment with EGFR-targeted mono-clonal antibodies[J].J Clin Oncol,2004,22:4772-4778.
• [20]Francoual M,Etienne-Grimaldi MC,Formento JL,et al.EGFR in colorectal cancer:more than a simple receptor[J].Ann Oncol,2006,17:962-967.
• [21]Moroni M,Veronese S,Benvenuti S,et al.Gene copy number for epidermal growth factor receptor(EGFR)and clinical response to antiEGFR treatmentin colorectal cancer:a cohort study[J].Lancet Oncol,2005,6:279-286.
• [22]Personeni N,Fieuws S,Piessevaux H,et al.Clinical use-fulness of EGFR gene copy number as a predictive marker in colorectal cancer patients treated with cetuximab:a fluores-cent in situ hybridization study[J].Clin Cancer Res,2008,14:5869-5876.
• [23]Lenz HJ,Van Cutsem E,Khambata-Ford S,et al.Multi-center phase II and translational study of cetuximab in meta-static colorectal carcinoma refractory to irinotecan,oxalipla-tin,and fluoropyrimidines[J].J Clin Oncol,2006,24:4914-4921.
• [24]Khambata-Ford S,Garrett CR,Meropol NJ,et al.Expres-sion of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer pa-tients treated with cetuximab[J].J Clin Oncol,2007,25:3230-3237.
• [25]Jacobs B,De Roock W,Piessevaux H,et al.Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in metastatic colorectal cancer treated with cetux-imab[J].J Clin Oncol,2009,27:5068-5074.