Cetuximab preclinical antitumor activity (monotherapy and combination based) is not predicted by relative total or activated epidermal growth factor receptor tumor expression levels
Cetuximab preclinical antitumor activity (monotherapy and combination based) is not predicted by relative total or activated epidermal growth factor receptor tumor expression levels
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DOI：
10.1158/1535-7163.mct-05-0259
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发表时间：
2006-01-01
影响因子：
5.7
通讯作者：
Rose, WC
中科院分区：
文献类型：
--
作者：
Wild, R;Fager, K;Rose, WC
尽管厄比妥（西妥昔单抗）在临床环境中已被证明具有治疗效益，但预测对该药物反应性的分子决定因素仍未得到很好的理解。在这里，我们评估了肿瘤中基础总和活化（pY1068）表皮生长因子受体（EGFR）水平与对西妥昔单抗单药治疗或基于联合治疗的反应性之间的关系。西妥昔单抗单独治疗（0.25-1 mg/只/只，q3d, i.p）可有效延缓GEO和L2987肿瘤生长至少10天，对应于log细胞杀伤值>= 1.0。在A549和WiDr异种移植物中可见交界性活性。然而，西妥昔单抗在HT29、HCT116、LOVO、col205、LX-1、HCC70和N87模型中未显示出任何显著的抗肿瘤活性。所有研究的肿瘤都有可检测到的但不同水平的EGFR。对于联合治疗方案，西妥昔单抗（1mg /小鼠/注射，q3dx5，腹腔注射）和顺铂（4.5 mg/kg/注射，q3dx5，静脉注射）在顺铂难治但西妥昔单抗应答的GEO肿瘤模型中，被证明比单个单药治疗更有效(P
Although Erbitux (cetuximab) has proven therapeutic benefit in the clinical setting, the molecular determinants predicting responsiveness to this agent are still not very well understood. Here, we assessed the relationship between basal total and activated (pY1068) epidermal growth factor receptor (EGFR) levels in a tumor and the responsiveness to cetuximab monotherapy or combination-based treatment using human xenograft models. Cetuximab treatment alone (0.25-1 mg/mouse/injection, q3d, i.p.) effectively delayed the growth of GEO and L2987 tumors by a minimum of 10 days corresponding to log cell kill values of >= 1.0. Borderline activity was seen in the A549 and WiDr xenografts. However, cetuximab failed to show any significant antitumor activity in the HT29, HCT116, LOVO, Colo205, LX-1, HCC70, and N87 models. All of the studied tumors had detectable yet variable levels of EGFR. For combination regimens, cetuximab (1 mg/mouse/injection, q3dx5, i.p.) and cisplatin (4.5 mg/kg/injection, q3dx5, i.v.) proved to be significantly more efficacious than individual monotherapies in the cisplatin-refractory yet cetuximab-responsive GEO tumor model (P