Wright Sarah Christine Elisabeth, Vasilevski Natali, Serra Violeta, Rodon Jordi, Eichhorn Pieter Johan Adam
Curtin Medical School, Faculty of Health Sciences, Curtin University, Bentley 6102, Australia.
Curtin Health Innovation Research Institute and Faculty of Health Sciences, Curtin University, Bentley 6102, Australia.
Cancers (Basel). 2021 Mar 26;13(7):1538. doi: 10.3390/cancers13071538.
The phosphatidylinositol-3-kinase (PI3K) pathway plays a central role in the regulation of several signalling cascades which regulate biological processes such as cellular growth, survival, proliferation, motility and angiogenesis. The hyperactivation of this pathway is linked to tumour progression and is one of the most common events in human cancers. Additionally, aberrant activation of the PI3K pathway has been demonstrated to limit the effectiveness of a number of anti-tumour agents paving the way for the development and implementation of PI3K inhibitors in the clinic. However, the overall effectiveness of these compounds has been greatly limited by inadequate target engagement due to reactivation of the pathway by compensatory mechanisms. Herein, we review the common adaptive responses that lead to reactivation of the PI3K pathway, therapy resistance and potential strategies to overcome these mechanisms of resistance. Furthermore, we highlight the potential role in changes in cellular plasticity and PI3K inhibitor resistance.
磷脂酰肌醇-3-激酶（PI3K）通路在多种信号级联反应的调控中起着核心作用，这些信号级联反应调控着细胞生长、存活、增殖、迁移和血管生成等生物学过程。该通路的过度激活与肿瘤进展相关，是人类癌症中最常见的事件之一。此外，PI3K通路的异常激活已被证明会限制多种抗肿瘤药物的疗效，为PI3K抑制剂在临床上的开发和应用铺平了道路。然而，由于补偿机制导致该通路重新激活，这些化合物的总体疗效受到靶点结合不足的极大限制。在此，我们综述了导致PI3K通路重新激活、治疗耐药性的常见适应性反应以及克服这些耐药机制的潜在策略。此外，我们强调了细胞可塑性变化和PI3K抑制剂耐药性中的潜在作用。
Zotero 插件
