The PI3K Pathway at the Crossroads of Cancer and the Immune System: Strategies for Next Generation Immunotherapy Combinations

被引：26

作者：

Collins, Dearbhaile C. ^{[1
]}

Chenard-Poirier, Maxime ^{[1
]}

Lopez, Juanita S. ^{[1
]}

机构：

[1] Royal Marsden Hosp, Inst Canc Res, Downs Rd, Sutton SM2 5PT, Surrey, England

来源：

CURRENT CANCER DRUG TARGETS | 2018年 / 18卷 / 04期

关键词：

PI3K inhibitors; immunotherapy; combination therapy; PI3K pathway; micro-environment; cancer; CHECKPOINT BLOCKADE THERAPY; PD-L1; EXPRESSION; CELL; INHIBITOR; MTOR; IDELALISIB; GROWTH; AKT; ACTIVATION; RESISTANCE;

D O I：

10.2174/1568009617666170927114440

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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.

引用

页码：355 / 364

页数：10

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