摘要
免疫疗法导致了一些恶性肿瘤治疗的范式转变,为一些晚期癌症患者提供了长期持久的反应。越来越多的研究已经确定了免疫系统与关键的致癌性生长因子通路之间的联系。磷酸肌醇3-激酶(PI3K)-AKT-mTOR级联在癌症中经常被高度活化,并且在包括肿瘤生长和存活在内的许多细胞过程中起着不可或缺的作用,并且可能成为对治疗的抗性的基础。在这篇综述中,我们首先总结了该途径抑制剂最初研究的两项关键性知识,包括免疫相关不良事件的概况,如结肠炎,转氨酶和肺炎,以及大多数靶向药物的感染发生率增加PI3K-AKT-mTOR途径。然后我们讨论了我们对该通路在肿瘤微环境中的作用以及对先天和适应性免疫反应的调节的理解的最新进展,并提出了与PI3K-网络抑制剂和癌症免疫疗法的协同组合策略。
关键词: PI3K抑制剂,免疫疗法,联合疗法,PI3K途径,微环境,癌症。
图形摘要
Current Cancer Drug Targets
Title:The PI3K Pathway at the Crossroads of Cancer and the Immune System: Strategies for Next Generation Immunotherapy Combinations
Volume: 18 Issue: 4
关键词: PI3K抑制剂,免疫疗法,联合疗法,PI3K途径,微环境,癌症。
摘要: Immunotherapy has led to a paradigm shift in the treatment of some malignancies, providing long-term, durable responses for a subset of patients with advanced cancers. Increasingly, research has identified links between the immune system and critical oncogenic growth factor pathways. The phosphoinositide 3-kinase (PI3K)-AKT-mTOR cascade is frequently hyperactivated in cancer, and plays an integral role in many cellular processes including tumour growth and survival and can underlie resistance to therapies.
In this review, we first summarize two key learnings from the initial studies of inhibitors of this pathway, including the profile of immune-related adverse events such as colitis, transaminitis and pneumonitis and the increased incidence of infections with the majority of agents that target the PI3K-AKT-mTOR pathway. We then discuss recent advances in our understanding of the role of this pathway in the tumour micro-environment, and in the regulation of innate and adaptive immune responses, and propose synergistic combination strategies with PI3K-network inhibitors and cancer immunotherapy.
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Cite this article as:
The PI3K Pathway at the Crossroads of Cancer and the Immune System: Strategies for Next Generation Immunotherapy Combinations, Current Cancer Drug Targets 2018; 18 (4) . https://dx.doi.org/10.2174/1568009617666170927114440
DOI https://dx.doi.org/10.2174/1568009617666170927114440 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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