CAJ | 학술논문

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(PI3K)-蛋白激酶B(AKT)通路扩增等有关.酪氨酸激酶抑制剂、PI3K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.
곡타주단항여화료약물련용후제고료인류표피생장인자수체(HER)2과표체유선암적반응솔,단재개시치료후수월역출현치료성내약,한제료환자적총생존기.곡타주단항내약궤제주요여HER가족이외적단백락안산격매수체신호통로활화、린지선기순3격매(PI3K)-단백격매B(AKT)통로확증등유관.락안산격매억제제、PI3K억제제등분자파향약물작위곡타주단항내약자적체대치료수단,단약료효균불심만의.다개대형림상시험증실,신형분자파향약물연합응용능명현한제심혹최종소제곡타주단항초시치료내약성문제.
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.