Abstract
The mammalian target of rapamycin (mTOR) kinase is positioned at the juncture of several pathways regulating cell growth and proliferation. It is the downstream effector of the oncogenic PI3K/Akt pathway and is a key regulator of translational initiation. Accumulating data support mTORs role in lymphomagenesis, and its inhibition in preclinical models leads to lymphoma regression. The rationale for testing mTOR inhibitors in patients with lymphoma is evident, and early clinical data is promising. Along with the prototype of mTOR inhibitors, rapamycin, there are three mTOR inhibitors furthest along in development: temsirolimus, everolimus, and AP23573. These agents are emerging as well-tolerated drugs with encouraging preliminary activity. Here we review the rationale for testing mTOR inhibitors in lymphoma, the phase 1 trials influencing dose and schedule of mTOR inhibitors, and summarize the clinical results in obtained to date in patients with lymphoma.
Keywords: mTOR, mTOR inhibitors, non-Hodgkin lymphoma, rapamycin, clinical trials, pharmacokinetics
Reviews on Recent Clinical Trials
Title: Clinical Development of mTOR Inhibitors: A Focus on Lymphoma
Volume: 2 Issue: 2
Author(s): Sonali M. Smith
Affiliation:
Keywords: mTOR, mTOR inhibitors, non-Hodgkin lymphoma, rapamycin, clinical trials, pharmacokinetics
Abstract: The mammalian target of rapamycin (mTOR) kinase is positioned at the juncture of several pathways regulating cell growth and proliferation. It is the downstream effector of the oncogenic PI3K/Akt pathway and is a key regulator of translational initiation. Accumulating data support mTORs role in lymphomagenesis, and its inhibition in preclinical models leads to lymphoma regression. The rationale for testing mTOR inhibitors in patients with lymphoma is evident, and early clinical data is promising. Along with the prototype of mTOR inhibitors, rapamycin, there are three mTOR inhibitors furthest along in development: temsirolimus, everolimus, and AP23573. These agents are emerging as well-tolerated drugs with encouraging preliminary activity. Here we review the rationale for testing mTOR inhibitors in lymphoma, the phase 1 trials influencing dose and schedule of mTOR inhibitors, and summarize the clinical results in obtained to date in patients with lymphoma.
Export Options
About this article
Cite this article as:
Smith M. Sonali, Clinical Development of mTOR Inhibitors: A Focus on Lymphoma, Reviews on Recent Clinical Trials 2007; 2 (2) . https://dx.doi.org/10.2174/157488707780599366
DOI https://dx.doi.org/10.2174/157488707780599366 |
Print ISSN 1574-8871 |
Publisher Name Bentham Science Publisher |
Online ISSN 1876-1038 |
- 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
-
Physical Activity and Diabetic Cardiomyopathy: Myocardial Adaptation Depending on Exercise Load
Current Diabetes Reviews The Drug Targeting and Delivery Approach Applied to Pt-Antitumour Complexes. A Coordination Point of View
Current Medicinal Chemistry Microarray Data Analysis: Current Practices and Future Directions
Current Pharmacogenomics Computer-Aided Drug Design of Bioactive Natural Products
Current Topics in Medicinal Chemistry Need to Think Outside Organ-based Diagnosis to Molecular Diagnostics
Applied Clinical Research, Clinical Trials and Regulatory Affairs Natural Products: A Rich Source of Antiviral Drug Lead Candidates for the Management of COVID-19
Current Pharmaceutical Design Energy Dependent Transport of Xenobiotics and Its Relevance to Multidrug Resistance
Current Cancer Drug Targets Erythropoietin in Cancer: An Update
Current Molecular Medicine Discovery of N-Phenyl-4-(1H-pyrrol-3-yl)pyrimidin-2-amine Derivatives as Potent Mnk2 Inhibitors: Design, Synthesis, SAR Analysis, and Evaluation of in vitro Anti-leukaemic Activity
Medicinal Chemistry QSPR and Flow Cytometry Analysis (QSPR-FCA): Review and New Findings on Parallel Study of Multiple Interactions of Chemical Compounds with Immune Cellular and Molecular Targets
Current Drug Metabolism Toxicological Profile of Therapeutic Nanodelivery Systems
Current Drug Metabolism Epigenome-Wide Association Studies (EWAS) in Cancer
Current Genomics Patients Characteristics and Clinical Implications of Suboptimal CD4 T-Cell Gains After 1 Year of Successful Antiretroviral Therapy
Current HIV Research A Review of Natural and Synthetic Antioxidants Important for Health and Longevity
Current Medicinal Chemistry Cardioprotective Effects of Natural Products <i>via</i> the Nrf2 Signaling Pathway
Current Vascular Pharmacology Reconceptualizing Adult Neurogenesis: Role for Sphingosine-1-Phosphate and Fibroblast Growth Factor-1 in Co-Ordinating Astrocyte-Neuronal Precursor Interactions
CNS & Neurological Disorders - Drug Targets A Review on PARP1 Inhibitors: Pharmacophore Modeling, Virtual and Biological Screening Studies to Identify Novel PARP1 Inhibitors
Current Topics in Medicinal Chemistry Clonetics
Current Drug Metabolism Lymphangiogenesis and Anti-Tumor Immune Responses
Current Molecular Medicine Metastatic Melanoma in a Young Woman Treated with TNF-Alpha Inhibitor for Psoriatic Arthritis: A Case Report
Current Drug Safety