Abstract
Membrane transporters play a role in determining the absorption, distribution, metabolism and excretion of small molecule anticancer drugs and mediating chemosensitivity and resistance of tumor cells to these drugs. Our understanding of the influence of these transporters on the pharmacokinetics, clinical effectiveness and tolerability has considerably increased in the last decade. We reviewed the interaction of the small molecule anticancer drugs approved in the last decade with the more common membranes transporters, such as ABCB1, ABCG2, and OATP. The drugs were divided into three categories: targeted therapies, cytotoxic agents and hormonal therapies. The literature appears to focus on the interaction of the targeted therapies compared to the remaining two categories. Furthermore, most data stemmed from nonclinical studies with only a few clinical examples where transporters corresponded with systemic exposure, clinical effectiveness, or tolerability. More nonclinical and clinical studies are needed to improve the ability to use the findings from these nonclinical studies to predict clinical outcomes, but the literature appears to be rapidly expanding as our understanding of these transporters grows. Therefore, determining the interaction of membrane transporters with small molecule anticancer drugs can facilitate the development of effective and safe treatments.
Keywords: Cytotoxic agents, drug resistance, drug-drug interactions, hormonal therapies, pharmacokinetics, targeted anticancer therapies, transporters
Anti-Cancer Agents in Medicinal Chemistry
Title: The Interactions of Anti-Cancer Drugs Approved in the Last Decade in the United States with Membrane Transporters
Volume: 10 Issue: 8
Author(s): Lokesh Jain, Sophia Abraham and Stacy S. Shord
Affiliation:
Keywords: Cytotoxic agents, drug resistance, drug-drug interactions, hormonal therapies, pharmacokinetics, targeted anticancer therapies, transporters
Abstract: Membrane transporters play a role in determining the absorption, distribution, metabolism and excretion of small molecule anticancer drugs and mediating chemosensitivity and resistance of tumor cells to these drugs. Our understanding of the influence of these transporters on the pharmacokinetics, clinical effectiveness and tolerability has considerably increased in the last decade. We reviewed the interaction of the small molecule anticancer drugs approved in the last decade with the more common membranes transporters, such as ABCB1, ABCG2, and OATP. The drugs were divided into three categories: targeted therapies, cytotoxic agents and hormonal therapies. The literature appears to focus on the interaction of the targeted therapies compared to the remaining two categories. Furthermore, most data stemmed from nonclinical studies with only a few clinical examples where transporters corresponded with systemic exposure, clinical effectiveness, or tolerability. More nonclinical and clinical studies are needed to improve the ability to use the findings from these nonclinical studies to predict clinical outcomes, but the literature appears to be rapidly expanding as our understanding of these transporters grows. Therefore, determining the interaction of membrane transporters with small molecule anticancer drugs can facilitate the development of effective and safe treatments.
Export Options
About this article
Cite this article as:
Jain Lokesh, Abraham Sophia and S. Shord Stacy, The Interactions of Anti-Cancer Drugs Approved in the Last Decade in the United States with Membrane Transporters, Anti-Cancer Agents in Medicinal Chemistry 2010; 10 (8) . https://dx.doi.org/10.2174/187152010794473966
DOI https://dx.doi.org/10.2174/187152010794473966 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
-
The Delicate Equilibrium between Oxidants and Antioxidants in Brain Glioma
Current Neuropharmacology Anti-miRNA-23a Oligonucleotide Suppresses Glioma Cells Growth by Targeting Apoptotic Protease Activating Factor-1
Current Pharmaceutical Design Adult Neural Stem Cell Therapy: Expansion In Vitro, Tracking In Vivo and Clinical Transplantation
Current Drug Targets Mitocans: Mitochondrial Targeted Anti-Cancer Drugs as Improved Therapies and Related Patent Documents
Recent Patents on Anti-Cancer Drug Discovery Antineoplastic Potential of Medicinal Plants
Recent Patents on Biotechnology Sphingolipids in Cell Signaling: Their Function as Receptor Ligands, Second Messengers, and Raft Constituents
Current Immunology Reviews (Discontinued) Tamoxifen as a Powerful Neuroprotectant in Experimental Stroke and Implications for Human Stroke Therapy
Recent Patents on CNS Drug Discovery (Discontinued) Flavonoids in Cancer Prevention
Anti-Cancer Agents in Medicinal Chemistry The Role of Shcbp1 in Signaling and Disease
Current Cancer Drug Targets Synthesis and Preliminary Evaluation of 5-[18F]fluoroleucine
Current Radiopharmaceuticals Combination of Phytochemicals as Adjuvants for Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Nanoparticle-Derived Non-Viral Genetic Transfection at the Blood-Brain Barrier to Enable Neuronal Growth Factor Delivery by Secretion from Brain Endothelium
Current Medicinal Chemistry P-Glycoprotein and Breast Cancer Resistance Protein Affect Disposition of Tandutinib, A Tyrosine Kinase Inhibitor
Drug Metabolism Letters Insulin-Like Growth Factor 2 - The Oncogene and its Accomplices
Current Pharmaceutical Design Analytical Approaches for Assaying Metallodrugs in Biological Samples: Recent Methodological Developments and Future Trends
Current Drug Metabolism Mechanisms of Drug Resistance in Cancer Chemotherapy: Coordinated Role and Regulation of Efflux Transporters and Metabolizing Enzymes
Current Pharmaceutical Design ADAMTS9-AS2: A Functional Long Non-coding RNA in Tumorigenesis
Current Pharmaceutical Design Targeting the L-Arginine-Nitric Oxide Pathway for Cancer Treatment
Current Pharmaceutical Design Obesity and Inflammation: Colorectal Cancer Engines
Current Molecular Pharmacology Advances and Challenges in the Use of Nanoparticles to Optimize PK/PD Interactions of Combined Anti-Cancer Therapies
Current Drug Metabolism