The PI3K Pathway at the Crossroads of Cancer and the Immune System: Strategies for Next Generation Immunotherapy Combinations.
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Date
2018-01Author
Collins, DC
Chenard-Poirier, M
Lopez, JS
Type
Journal Article
Metadata
Show full item recordAbstract
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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Subject
Animals
Humans
Neoplasms
Immunotherapy
Signal Transduction
Immunity, Cellular
Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinase
TOR Serine-Threonine Kinases
Phosphoinositide-3 Kinase Inhibitors
Research team
Medicine (de Bono Prostate)
Language
eng
Date accepted
2017-07-03
License start date
2018-01
Citation
Current cancer drug targets, 2018, 18 (4), pp. 355 - 364