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
-
Targeted Drug Delivery to Central Nervous System (CNS) for the Treatment of Neurodegenerative Disorders: Trends and Advances
Central Nervous System Agents in Medicinal Chemistry Medicinal Chemistry of the Epigenetic Diet and Caloric Restriction
Current Medicinal Chemistry Targeting SKCa Channels in Cancer: Potential New Therapeutic Approaches
Current Medicinal Chemistry Diffusion-Weighted MRI for Assessment of Early Cancer Treatment Response
Current Pharmaceutical Biotechnology A Retrospective Study on the Incidence of Seizures among Neurosurgical Patients Who Treated with Imipenem/Cilastatin or Meropenem
Current Pharmaceutical Biotechnology Potentials of ES Cell Therapy in Neurodegenerative Diseases
Current Pharmaceutical Design Signaling Pathways Involved in Neuron-Astrocyte Adhesion and Migration
Current Molecular Medicine Gold Nanoparticles in Cancer Therapy: Efficacy, Biodistribution, and Toxicity
Current Pharmaceutical Design Statins and Alkylphospholipids as New Anticancer Agents Targeting Lipid Metabolism
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Targeting of Malignant Glioma
Anti-Cancer Agents in Medicinal Chemistry DNMT Inhibitors in Cancer, Current Treatments and Future Promising Approach: Inhibition of Specific DNMT-Including Complexes
Epigenetic Diagnosis & Therapy (Discontinued) Is the Epithelial-to-Mesenchymal Transition Clinically Relevant for the Cancer Patient?
Current Pharmaceutical Biotechnology The Role of Phenolic Compounds in the Fight against Cancer – A Review
Anti-Cancer Agents in Medicinal Chemistry Recent Developments in Boron Neutron Capture Therapy (BNCT) Driven by Nanotechnology
Current Chemical Biology Prognostic and Predictive Biomarkers in Cancer
Current Cancer Drug Targets Toll-Like Receptors: Cost or Benefit for Cancer?
Current Pharmaceutical Design Exploring the Role of Nerve Growth Factor in Multiple Sclerosis: Implications in Myelin Repair
CNS & Neurological Disorders - Drug Targets Recent Research Progress on Magnetic Nanocomposites with Silica Shell Structures Preparation and Nanotheranostic Applications
Recent Patents on Nanotechnology MicroRNA-7 Regulates Insulin Signaling Pathway by Targeting IRS1, IRS2, and RAF1 Genes in Gestational Diabetes Mellitus
MicroRNA MicroRNAs-Based Therapeutic Strategy for Virally Induced Diseases
Current Drug Discovery Technologies