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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Lipidomic Analysis of Glioblastoma Multiforme Using Mass Spectrometry
Current Metabolomics A Transporter Gene (Sodium Iodide Symporter) for Dual Purposes in Gene Therapy: Imaging and Therapy
Current Gene Therapy Induction of Tumour Cell Senescence: A New Strategy in Anticancer Treatment
Medicinal Chemistry Reviews - Online (Discontinued) Context-dependent Action of Transforming Growth Factor β Family Members on Normal and Cancer Stem Cells
Current Pharmaceutical Design “Letting the Air In” Can Set the Stage for Tumor Recurrences
Current Cancer Therapy Reviews Meet Our Associate Editor
Current Bioactive Compounds Recent Progress in Discovery and Development of Antimitotic Agents
Anti-Cancer Agents in Medicinal Chemistry Glycogen Metabolism and Brain Pathologies
Central Nervous System Agents in Medicinal Chemistry Small Molecule Integrin Antagonists in Cancer Therapy
Mini-Reviews in Medicinal Chemistry Brain Tumor Segmentation Using Deep Belief Networks and Pathological Knowledge
CNS & Neurological Disorders - Drug Targets Ginkgolic Acids Confer Potential Anticancer Effects by Targeting Pro- Inflammatory and Oncogenic Signaling Molecules
Current Molecular Pharmacology Editorial [ The Role of Epidermal Growth Factor Receptor (EGFR) Targeting Drugs in the Treatment of Cancer Guest Editor: Fortunato Ciardiello ]
Current Cancer Therapy Reviews Protective Role of Natural Products in Glioblastoma Multiforme: A Focus on Nitric Oxide Pathway
Current Medicinal Chemistry Immunotoxins Constructed with Ribosome-Inactivating Proteins and their Enhancers: A Lethal Cocktail with Tumor Specific Efficacy
Current Pharmaceutical Design Integrative Analysis of miRNA-mediated Competing Endogenous RNA Network Reveals the lncRNAs-mRNAs Interaction in Glioblastoma Stem Cell Differentiation
Current Bioinformatics Network Pharmacology and Reverse Molecular Docking-Based Prediction of the Molecular Targets and Pathways for Avicularin Against Cancer
Combinatorial Chemistry & High Throughput Screening Chlorella vulgaris Induces Apoptosis of Human Non-Small Cell Lung Carcinoma (NSCLC) Cells
Medicinal Chemistry Dendritic Cells in Esophageal Adenocarcinoma: The Currently Available Information and Possibilities to use Dendritic Cells for Immunotherapeutic Approaches
Current Pharmaceutical Design Progress on Multi-Modality Molecular Imaging
Current Medical Imaging An Overview on the Role of miR-451 in Lung Cancer: Diagnosis, Therapy, and Prognosis
MicroRNA