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
-
The Role of the Endoplasmic Reticulum in the Accumulation of β-Amyloid Peptide in Alzheimers Disease
Current Molecular Medicine Beyond RAS: The Role of Epidermal Growth Factor Receptor (EGFR) and its Network in the Prediction of Clinical Outcome During Anti-EGFR Treatment in Colorectal Cancer Patients
Current Drug Targets Oncolytic Viruses: The Best is Yet to Come
Current Cancer Drug Targets The Use of Herbal Medicine in Cancer-related Anorexia/ Cachexia Treatment Around the World
Current Pharmaceutical Design TNF-Related Apoptosis-Inducing Ligand (TRAIL) as a Pro-Apoptotic Signal Transducer with Cancer Therapeutic Potential
Current Pharmaceutical Design Metabotropic Purinergic Receptors in Lipid Membrane Microdomains
Current Medicinal Chemistry Anti-cancer and Anti-angiogenic Properties of Various Natural Pentacyclic Tri-terpenoids and Some of their Chemical Derivatives
Current Organic Chemistry Epidermal Growth Factor Receptor and its Trafficking Regulation by Acetylation: Implication in Resistance and Exploring the Newer Therapeutic Avenues in Cancer
Current Topics in Medicinal Chemistry Pharmacological Aspects of the Enzastaurin-Pemetrexed Combination in Non-Small Cell Lung Cancer (NSCLC)
Current Drug Targets The Action of Prostaglandins on Ion Channels
Current Neuropharmacology Endogenous Events Modulating Myogenic Regulation of Cerebrovascular Function
Current Vascular Pharmacology Lipid Based Anti-Retroviral Nanocarriers: A Review of Current Literature and Ongoing Studies
Drug Delivery Letters Recent Developments in Chimeric NSAIDs as Anticancer Agents: Teaching an Old Dog a New Trick
Mini-Reviews in Medicinal Chemistry G and C Iterons and Strings in MicroRNAs Should be Important in Regulation of mRNAs<sup>†</sup>
MicroRNA Polo-Like Kinases (Plks) are Prognostic Markers for Gynecologic Malignancies
Current Women`s Health Reviews An Insight into Drug Repositioning for the Development of Novel Anti-Cancer Drugs
Current Topics in Medicinal Chemistry Dasatinib: An Anti-Tumour Agent via Src Inhibition
Current Drug Targets MR Spectroscopy in Metabolic Profiling Studies of Stem Cells
Current Medical Imaging Lipid Metabolism and Mitochondria: Cross Talk in Cancer
Current Drug Targets Drug Delivery Systems for Imaging and Therapy of Parkinson's Disease
Current Neuropharmacology