HER2过表达乳腺癌曲妥珠单抗耐药后靶向治疗策略  

Targeted treatment strategies for patients with trastuzumab-resistant HER2-overexpressing breast cancer

作　　者：周正仕[1] 廖小方[1] 

机构地区：[1]浙江省衢州市人民医院放疗科,324000

出　　处：《国际肿瘤学杂志》2012年第4期278-281,共4页Journal of International Oncology

摘　　要：曲妥珠单抗与化疗药物联用后提高了人类表皮生长因子受体（HER）2过表达乳腺癌的反应率，但在开始治疗后数月易出现治疗性耐药，限制了患者的总生存期。曲妥珠单抗耐药机制主要与HER家族以外的蛋白酪氨酸激酶受体信号通路活化、磷脂酰肌醇3激酶（P13K）-蛋白激酶B（AKT）通路扩增等有关。酪氨酸激酶抑制剂、P13K抑制剂等分子靶向药物作为曲妥珠单抗耐药者的替代治疗手段，单药疗效均不甚满意。多个大型临床试验证实，新型分子靶向药物联合应用能明显限制甚或最终消除曲妥珠单抗初始治疗耐药性问题。Trastuzumab combined with chemotherapy improves overall response rate in women with HER2-overexpressing breast cancer. However, therapeutic resistance to trastuzumab typically occurs after several months of starting therapy and overall survival does not improve significantly. Studies have reported that the potential mechanisms of resistance to trastuzumab are mainly related to the signal pathway activation from receptor tyrosine protein kinases outside of the HER family and the amplification of the PI3K-AKT pathway. Novel target therapies such as tyrosine kinase inhibitors, PI3K inhibitors are approved as substitutes for the treatment of HER2-overexpressing breast cancer, but the response to each single-agent tends to be short-lived. Several large randomized adjuvant trials have showed that novel molecular targeted therapies combinations will markedly limit or eventually abrogate acquired resistance to primary trastuzumab therapy.

关 键 词：受体 表皮生长因子 乳腺肿瘤 抗药性 

分 类 号：R737.9[医药卫生—肿瘤]