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摘要
目的:在这篇叙述性综述中,我们总结了PI3K-AKTmTOR(PAM)途径在卵巢癌和子宫内膜癌中的作用和意义,提供了有关该主题的最新和相关文献,并探讨了靶向PAM的选择以及药物开发的未来前景。背景:PAM途径的改变在子宫内膜癌和卵巢癌中都很常见,并且在特定的组织学定义亚型中有描述。 PAM似乎参与了子宫内膜和卵巢癌变的关键步骤,通常以机械方式参与了治疗耐药性表型的获得,该表型可能是可靶向的。但是,早期使用PAMinhibitors(PAMi)进行的临床试验提供了令人失望的结果,尤其是在未经选择的人群中测试了非同种型特异性抑制剂时,伴随着不良的安全性。从那时起,当使用更具选择性的药物靶向PAM蛋白的特定同工型时,收集到了更多令人鼓舞的观察结果,从而获得了令人鼓舞的活性和更可控的毒性。结论:尽管在一些有希望的临床前研究中已经证明了抑制PAM途径的原理,但尚无III期临床试验可证明PAM抑制剂的显着益处。管理靶向药物的一种方法是针对最有可能获得可观收益的特定亚人群调整其使用,即采用个体化的精准医学方法。
关键词: PI3K-AKT-mTOR途径,精密医学,靶向治疗,卵巢癌,子宫内膜癌,妇科癌,铂电阻
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