Abstract
The PI3K/Akt/mTOR signaling pathway plays a key role in diverse physiologic processes. It is also central to many aspects of the malignant process. Genetic phenomena that lead to constitutive pathway activation are common in human cancer; the most relevant are mutations affecting the catalytic subunit of PI3K and loss of function of the PTEN tumor suppressor. These factors have made this important cascade attractive as a potential target for cancer therapeutics. A host of inhibitors are now in various stages of development that target key nodes within the PI3K pathway. To date, however, the efficacy of these agents has fallen short of expectation, with at least one possible explanation being the presence of feedback loops and cross-talk that exists within and between PI3K and other signaling pathways. Accordingly, enthusiasm is again high as strategies employing therapeutic combinations are gaining pace, with encouraging results documented in both preclinical studies and emerging clinical trials. Here, we review the agents that have reached evaluation in early phase clinical studies of human subjects with cancer, and discuss the rationale for and use of novel drug combinations.
Keywords: PI3K, PIK3CA, PTEN, mTOR, Akt, PI3K inhibitor, therapeutic combination, clinical trial, signaling pathway, tumor suppressor
Current Pharmaceutical Design
Title:PI3K Pathway Inhibitors: Better Not Left Alone
Volume: 19 Issue: 5
Author(s): Ben Markman, Jessica J. Tao and Maurizio Scaltriti
Affiliation:
Keywords: PI3K, PIK3CA, PTEN, mTOR, Akt, PI3K inhibitor, therapeutic combination, clinical trial, signaling pathway, tumor suppressor
Abstract: The PI3K/Akt/mTOR signaling pathway plays a key role in diverse physiologic processes. It is also central to many aspects of the malignant process. Genetic phenomena that lead to constitutive pathway activation are common in human cancer; the most relevant are mutations affecting the catalytic subunit of PI3K and loss of function of the PTEN tumor suppressor. These factors have made this important cascade attractive as a potential target for cancer therapeutics. A host of inhibitors are now in various stages of development that target key nodes within the PI3K pathway. To date, however, the efficacy of these agents has fallen short of expectation, with at least one possible explanation being the presence of feedback loops and cross-talk that exists within and between PI3K and other signaling pathways. Accordingly, enthusiasm is again high as strategies employing therapeutic combinations are gaining pace, with encouraging results documented in both preclinical studies and emerging clinical trials. Here, we review the agents that have reached evaluation in early phase clinical studies of human subjects with cancer, and discuss the rationale for and use of novel drug combinations.
Export Options
About this article
Cite this article as:
Markman Ben, J. Tao Jessica and Scaltriti Maurizio, PI3K Pathway Inhibitors: Better Not Left Alone, Current Pharmaceutical Design 2013; 19 (5) . https://dx.doi.org/10.2174/1381612811306050895
DOI https://dx.doi.org/10.2174/1381612811306050895 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- 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
- Announcements
Related Articles
-
Generation of Human Cardiomyocytes for Cardiac Regenerative Therapies: Differentiation and Direct Reprogramming
Current Pharmaceutical Design Statins and Oxidative Stress in the Cardiovascular System
Current Pharmaceutical Design Understanding Abnormal c-JNK/p38MAPK Signaling in Amyotrophic Lateral Sclerosis: Potential Drug Targets and Influences on Neurological Disorders
CNS & Neurological Disorders - Drug Targets Targeting Prenylated RAS Modifying Enzymes in Cancer Cells
Current Signal Transduction Therapy Is Nephrogenic Systemic Fibrosis a Disease of Fibrocytes?
Current Rheumatology Reviews Studying the Ethno-Pharmacological Basis of Antiepileptic Activity of Medhya Rasayanas- A Nootropic Package From Ayurveda
Current Traditional Medicine Thiopurine Biotransformation and Pharmacological Effects: Contribution of Oxidative Stress
Current Drug Metabolism Approaches for Administering Chemotherapy in the Intensive Care Unit
Current Drug Safety GRK2 Inhibition in Heart Failure: Something Old, Something New
Current Pharmaceutical Design In Vivo Delivery of Morpholino Oligos by Cell-Penetrating Peptides
Current Pharmaceutical Design Mitochondrial genome sequencing in atherosclerosis: what's next?
Current Pharmaceutical Design Gene Therapy Approaches for Cardiovascular Diseases
Current Gene Therapy Cardiac Multidetector Computed Tomography: Basic Physics of Image Acquisition and Clinical Applications
Current Cardiology Reviews Cardiac and Vascular Impairment in Patients with Mild Psoriasis: A Longitudinal Study
Current Vascular Pharmacology Acetylome Regulation by Sirtuins in the Brain: From Normal Physiology to Aging and Pathology
Current Pharmaceutical Design Tissue Protective and Anti-Fibrotic Actions of Suramin: New Uses of an Old Drug
Current Clinical Pharmacology Cardiac Tumors: Clinical Perspective and Therapeutic Considerations
Current Drug Targets ErbB4 and its Isoforms: Patentable Drug Targets?
Recent Patents on DNA & Gene Sequences Acute Respiratory Failure in Obstetric Patients
Current Women`s Health Reviews Glucocorticoids and the Cardiovascular System: State of the Art
Current Pharmaceutical Design