Abstract
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.
Keywords: PI3K inhibitors, immunotherapy, combination therapy, PI3K pathway, micro-environment, cancer.
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
Author(s): Dearbhaile C. Collins, Maxime Chenard-Poirier and Juanita S. Lopez*
Affiliation:
- Institute of Cancer Research, Royal Marsden Hospital, Downs Road, Sutton, SM2 5PT, London,United Kingdom
Keywords: PI3K inhibitors, immunotherapy, combination therapy, PI3K pathway, micro-environment, cancer.
Abstract: 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:
Collins C. Dearbhaile, Chenard-Poirier Maxime and Lopez S. Juanita*, 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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