在伊立替康耐药的结直肠癌中联合靶向治疗（西妥昔单抗、贝伐珠单抗）的分子预测因子（BOND-2 研究）。
Molecular predictors of combination targeted therapies (cetuximab, bevacizumab) in irinotecan-refractory colorectal cancer (BOND-2 study).
机构信息
Division of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90033, USA.
出版信息
Anticancer Res. 2010 Oct;30(10):4209-17.
BACKGROUND
To test whether intratumoral gene expression levels and germline polymorphisms predict clinical outcome in metastatic colorectal cancer (mCRC) patients treated with cetuximab and bevacizumab plus irinotecan (CBI) vs. cetuximab and bevacizumab (CB)(BOND2).
PATIENTS AND METHODS
Genomic DNA was extracted for genotyping from 65 patients (31: CBI arm and 34: CB arm). Thirty five patients had tissue samples available for the gene expression assay (18: CBI arm and 17: CB arm).
RESULTS
High intratumoral gene expression levels of EGFR, VEGFR2 and NRP1 were associated with longer overall survival (OS) in patients receiving combined monoclonal antibodies with or without irinotecan. FCGR3A V158F, CyclinD1 A870G and EGFR R497K polymorphisms are associated with clinical outcome in patients received combined cetuximab and bevacizumab.
CONCLUSIONS
Intratumoral gene expression levels of EGFR, VEGFR2 and NRP as well as polymorphisms in FCGR3A, CyclinD1 and EGFR could predict clinical outcome in mCRC patients enrolled in BOND2, independent of KRAS mutation status.
背景
为了检测在接受西妥昔单抗联合贝伐珠单抗加伊立替康（CBI）与西妥昔单抗联合贝伐珠单抗（CB）（BOND2）治疗的转移性结直肠癌（mCRC）患者中，肿瘤内基因表达水平和种系多态性是否可以预测临床结局，我们进行了此项研究。
患者与方法
对 65 名患者（31 名：CBI 组，34 名：CB 组）的基因组 DNA 进行基因分型。有 35 名患者的组织样本可用于基因表达检测（18 名：CBI 组，17 名：CB 组）。
结果
在接受联合单克隆抗体治疗的患者中，高肿瘤内 EGFR、VEGFR2 和 NRP1 的基因表达水平与总生存期（OS）延长相关。FCGR3A V158F、CyclinD1 A870G 和 EGFR R497K 多态性与接受西妥昔单抗联合贝伐珠单抗治疗的患者的临床结局相关。
结论
BOND2 研究中，无论 KRAS 突变状态如何，EGFR、VEGFR2 和 NRP1 的肿瘤内基因表达水平以及 FCGR3A、CyclinD1 和 EGFR 中的多态性都可以预测 mCRC 患者的临床结局。
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