Abstract
The phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR pathway is one of the most frequently activated signaling pathways in prostate cancer cells, and loss of the tumor suppressor PTEN and amplification of PIK3CA are the two most commonly detected mechanisms for the activation of these pathways. Aberrant activation of PI3K/Akt/mTOR has been implicated not only in the survival and metastasis of prostate cancer cells but also in the development of drug resistance. As such, selective inactivation of this pathway may provide opportunities to attack prostate cancer from all fronts. However, while preclinical studies examining specific inhibitors of PI3K or mTOR have yielded promising results, the evidence from clinical trials is less convincing. Emerging evidence from the analyses of some solid tumors suggests that a class of dual PI3K/mTOR inhibitors, which bind to and inactivate both PI3K and mTOR, may achieve better anti-cancer outcomes. In this review, we will summarize the mechanisms of action of these inhibitors, their effectiveness when used alone or in combination with other chemotherapeutic compounds, and their potential to serve as the next generation therapies for prostate cancer patients, particularly those who are resistant to the frontline chemotherapeutic drugs.
Keywords: Drug resistant, PI3K, mTOR, prostate cancer.
Current Medicinal Chemistry
Title:Targeting Drug-Resistant Prostate Cancer with Dual PI3K/mTOR Inhibition
Volume: 21 Issue: 26
Author(s): K.D. Tang and Ming-Tat Ling
Affiliation:
Keywords: Drug resistant, PI3K, mTOR, prostate cancer.
Abstract: The phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR pathway is one of the most frequently activated signaling pathways in prostate cancer cells, and loss of the tumor suppressor PTEN and amplification of PIK3CA are the two most commonly detected mechanisms for the activation of these pathways. Aberrant activation of PI3K/Akt/mTOR has been implicated not only in the survival and metastasis of prostate cancer cells but also in the development of drug resistance. As such, selective inactivation of this pathway may provide opportunities to attack prostate cancer from all fronts. However, while preclinical studies examining specific inhibitors of PI3K or mTOR have yielded promising results, the evidence from clinical trials is less convincing. Emerging evidence from the analyses of some solid tumors suggests that a class of dual PI3K/mTOR inhibitors, which bind to and inactivate both PI3K and mTOR, may achieve better anti-cancer outcomes. In this review, we will summarize the mechanisms of action of these inhibitors, their effectiveness when used alone or in combination with other chemotherapeutic compounds, and their potential to serve as the next generation therapies for prostate cancer patients, particularly those who are resistant to the frontline chemotherapeutic drugs.
Export Options
About this article
Cite this article as:
Tang K.D. and Ling Ming-Tat, Targeting Drug-Resistant Prostate Cancer with Dual PI3K/mTOR Inhibition, Current Medicinal Chemistry 2014; 21 (26) . https://dx.doi.org/10.2174/0929867321666140414100127
DOI https://dx.doi.org/10.2174/0929867321666140414100127 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
- Announcements
Related Articles
-
Roles of Histone Deacetylases in Angiogenic Cellular Processes
Current Angiogenesis (Discontinued) A Comprehensive Overview of Targeted Therapy in Metastatic Renal Cell Carcinoma
Current Cancer Drug Targets Evaluation of the in vivo Safety Profiles of Rictor Inhibition Using a Zebrafish Model
Current Pharmaceutical Design The Urokinase Receptor in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Impact on DNA Methylation in Cancer Prevention and Therapy by Bioactive Dietary Components
Current Medicinal Chemistry DNA Methyltransferases Inhibitors from Natural Sources
Current Topics in Medicinal Chemistry Inhibitors of HIV-1 Protease: Current State of the Art 10 Years After their Introduction. From Antiretroviral Drugs to Antifungal, Antibacterial and Antitumor Agents Based on Aspartic Protease Inhibitors
Current Medicinal Chemistry Marine Collagen as a Source of Bioactive Molecules: A Review
The Natural Products Journal Boronic Acid-based Enzyme Inhibitors: A Review of Recent Progress
Current Medicinal Chemistry Mycotherapy of Cancer: An Update on Cytotoxic and Antitumor Activities of Mushrooms, Bioactive Principles and Molecular Mechanisms of their Action
Current Topics in Medicinal Chemistry Recent Advances of Small Molecule Focal Adhesion Kinase (FAK) Inhibitors as Promising Anticancer Therapeutics
Current Medicinal Chemistry Anti-Cancer Approach with NK4: Bivalent Action and Mechanisms
Anti-Cancer Agents in Medicinal Chemistry From Amino Acids to Proteins as Targets for Metal-based Drugs
Current Drug Metabolism MicroRNAs as Therapeutic Targets for Anticancer Drugs in Lung Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry The Role of Melatonin in Multiple Sclerosis, Huntington's Disease and Cerebral Ischemia
CNS & Neurological Disorders - Drug Targets The Role of Cytokine Network in the Pathophysiology of Schizophrenia
Current Psychiatry Reviews Effect of Selenium-Saturated Bovine Lactoferrin (Se-bLF) on Antioxidant Enzyme Activities in Human Gut Epithelial Cells Under Oxidative Stress
Anti-Cancer Agents in Medicinal Chemistry Synthesis and Anti-Proliferative Activity of New Biphenyle-Benzylidenethiazolidine- 2,4-dione Bis-Adducts Containing Various Heterocyclic Cores
Letters in Drug Design & Discovery Thiazolidinedione: A Privileged Scaffold for the Development of Anticancer Agents
Current Topics in Medicinal Chemistry Alternative Splicing, DNA Damage and Modulating Drugs in Radiation Therapy for Cancer
Anti-Cancer Agents in Medicinal Chemistry