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AKT in cancer: new molecular insights and advances in drug development

机译:AKT治疗癌症:新的分子见解和药物开发进展

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The phosphatidylinositol-3 kinase (PI3K)-AKT pathway is one of the most commonly dysregulated pathways in all of cancer, with somatic mutations, copy number alterations, aberrant epigenetic regulation and increased expression in a number of cancers. The carefully maintained homeostatic balance of cell division and growth on one hand, and programmed cell death on the other, is universally disturbed in tumorigenesis, and downstream effectors of the PI3K-AKT pathway play an important role in this disturbance. With a wide array of downstream effectors involved in cell survival and proliferation, the well-characterized direct interactions of AKT make it a highly attractive yet elusive target for cancer therapy. Here, we review the salient features of this pathway, evidence of its role in promoting tumorigenesis and recent progress in the development of therapeutic agents that target AKT.
机译:磷脂酰肌醇3激酶(PI3K)-AKT途径是所有癌症中最常见的失调途径之一,在许多癌症中具有体细胞突变,拷贝数改变,异常的表观遗传调控和表达增加。一方面,精心维持的细胞分裂和生长的稳态平衡,另一方面是程序性的细胞死亡,在肿瘤发生中普遍受到干扰,PI3K-AKT途径的下游效应子在这种干扰中起重要作用。 AKT具有广泛的参与细胞存活和增殖的下游效应子,其特征明确的直接相互作用使其成为癌症治疗中极具吸引力但难以捉摸的靶标。在这里,我们回顾了该途径的显着特征,其在促进肿瘤发生中作用的证据以及在靶向AKT的治疗剂的开发中的最新进展。

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