Abstract
Endometrial cancer is the third most common cancer in women. Endometrial carcinomas (EC) are clinic histologically classified into two types. Type I tumours, which account for 80% of ECs, are estrogen-dependent and are low grade. Type II tumours are more aggressive with invasion into myometrium. Recently a new classification for endometrial cancer has been proposed based on molecular markers. Whether this classification is helpful for clinical management of endometrial cancer remains to be tested. At present, treatment outcomes of endometrial cancer are not satisfactory. Therefore, more effective approaches are sought. This review summarizes the recent studies about activation of PI3K/Akt pathway in EC and therapeutic implications of the inhibitors of the pathways with emphasis on dual inhibitors of PI3K and mTOR. Both genetic defects and environmental factors are involved in carcinogenesis and progression of EC via activation of multiple signal pathways including the PI3K/Akt pathway. Mutations of major components of the PI3K/Akt pathway are common in EC. Type I tumours usually have mutations in Ras, PTEN, PIK3CA, AKT1, beta-catenin and type II tumours have mutations in TP53. Environmental factor like obesity can also activate the PI3K/Akt pathway to increase the incidence of EC and to cause poorer prognosis. Therefore, inhibition of the PI3K/Akt pathway can be used for therapy of the disease. At present, mTOR inhibitors have been extensively studied and tested in clinical trials. A newly synthesised dual inhibitor of PI3K and mTOR BEZ235 has been shown to be more effective than mTOR inhibitor rapamycin. BEZ235 can inhibit feedback activation of PI3K/Akt pathway by rapamycin. It is promising to include effective PI3K/Akt inhibitors in current treatment regime of endometrial cancer to improve the therapeutic efficacy.
Keywords: Endometrial cancer, PI3K/Akt, PIK3CA, PTEN, Ras.
Current Medicinal Chemistry
Title:Activation of PI3K/Akt/mTOR Pathway and Dual Inhibitors of PI3K and mTOR in Endometrial Cancer
Volume: 21 Issue: 26
Author(s): Jiezhong Chen, Kong-Nan Zhao, Rui Li, Renfu Shao and Chen Chen
Affiliation:
Keywords: Endometrial cancer, PI3K/Akt, PIK3CA, PTEN, Ras.
Abstract: Endometrial cancer is the third most common cancer in women. Endometrial carcinomas (EC) are clinic histologically classified into two types. Type I tumours, which account for 80% of ECs, are estrogen-dependent and are low grade. Type II tumours are more aggressive with invasion into myometrium. Recently a new classification for endometrial cancer has been proposed based on molecular markers. Whether this classification is helpful for clinical management of endometrial cancer remains to be tested. At present, treatment outcomes of endometrial cancer are not satisfactory. Therefore, more effective approaches are sought. This review summarizes the recent studies about activation of PI3K/Akt pathway in EC and therapeutic implications of the inhibitors of the pathways with emphasis on dual inhibitors of PI3K and mTOR. Both genetic defects and environmental factors are involved in carcinogenesis and progression of EC via activation of multiple signal pathways including the PI3K/Akt pathway. Mutations of major components of the PI3K/Akt pathway are common in EC. Type I tumours usually have mutations in Ras, PTEN, PIK3CA, AKT1, beta-catenin and type II tumours have mutations in TP53. Environmental factor like obesity can also activate the PI3K/Akt pathway to increase the incidence of EC and to cause poorer prognosis. Therefore, inhibition of the PI3K/Akt pathway can be used for therapy of the disease. At present, mTOR inhibitors have been extensively studied and tested in clinical trials. A newly synthesised dual inhibitor of PI3K and mTOR BEZ235 has been shown to be more effective than mTOR inhibitor rapamycin. BEZ235 can inhibit feedback activation of PI3K/Akt pathway by rapamycin. It is promising to include effective PI3K/Akt inhibitors in current treatment regime of endometrial cancer to improve the therapeutic efficacy.
Export Options
About this article
Cite this article as:
Chen Jiezhong, Zhao Kong-Nan, Li Rui, Shao Renfu and Chen Chen, Activation of PI3K/Akt/mTOR Pathway and Dual Inhibitors of PI3K and mTOR in Endometrial Cancer, Current Medicinal Chemistry 2014; 21 (26) . https://dx.doi.org/10.2174/0929867321666140414095605
DOI https://dx.doi.org/10.2174/0929867321666140414095605 |
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
-
Between Bench and Bed Side: PI3K Inhibitors
Current Molecular Pharmacology 2-Deoxy-D-Ribose, a Downstream Mediator of Thymidine Phosphorylase, Regulates Tumor Angiogenesis and Progression
Anti-Cancer Agents in Medicinal Chemistry Isoprenylation of Intracellular Proteins as a New Target for the Therapy of Human Neoplasms: Preclinical and Clinical Implications
Current Drug Targets Subcellular Imaging and Diagnosis of Cancer using Engineered Nanoparticles
Current Pharmaceutical Design The Adenine Nucleotide Translocase 2, a Mitochondrial Target for Anticancer Biotherapy
Current Drug Targets Type 1 11 β-hydroxysteroid Dehydrogenase as Universal Drug Target in Metabolic Diseases?
Endocrine, Metabolic & Immune Disorders - Drug Targets Induction of Apoptosis by Curcumin and Its Implications for Cancer Therapy
Current Cancer Drug Targets Emodin Enhances the Chemosensitivity of Endometrial Cancer by Inhibiting ROS-Mediated Cisplatin-resistance
Anti-Cancer Agents in Medicinal Chemistry CEBP Epigenetic Dysregulation as a Drug Target for the Treatment of Hematologic and Gynecologic Malignancies
Current Drug Targets Fibroblast Growth Factor-2, Bone Homeostasis and Fracture Repair
Current Pharmaceutical Design Phytoestrogen-Rich Dietary Supplements in Anti-Atherosclerotic Therapy in Postmenopausal Women
Current Pharmaceutical Design Recent Developments of Steroid Sulfatase Inhibitors as Anti-Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry Female Infertility and Assisted Reproduction: Impact of Oxidative Stress-- An Update
Current Women`s Health Reviews Pleiotropic Effects of Fenofibrate
Current Pharmaceutical Design The Role of Estrogen and Estrogen-Related Drugs in Cardiovascular Diseases
Current Drug Metabolism Inhibition of Autophagy Strengthens Celastrol-Induced Apoptosis in Human Pancreatic Cancer In Vitro and In Vivo Models
Current Molecular Medicine Dietary Approaches and Alternative Therapies for Polycystic Ovary Syndrome
Current Nutrition & Food Science Alpha-1-Adrenergic Receptor Blockade Modifies Insulin-Regulated Aminopeptidase (IRAP) Activity in Rat Prostate and Modulates Oxytocin Functions
Drug Metabolism Letters Anti-inflammatory Phytochemicals for Chemoprevention of Colon Cancer
Current Cancer Drug Targets Endothelial Cell Senescence and Inflammaging: MicroRNAs as Biomarkers and Innovative Therapeutic Tools
Current Drug Targets