Abstract
Brain cancer is a devastating disease. Despite extensive research, treatment of brain tumors has been largely ineffective and the diagnosis of brain cancer remains uniformly fatal. Failure of brain cancer treatment may be in part due to limitations in drug delivery, influenced by the ABC drug efflux transporters P-gp and BCRP at the blood-brain and blood-tumor barriers, in brain tumor cells, as well as in brain tumor stem-like cells. P-gp and BCRP limit various anti-cancer drugs from entering the brain and tumor tissues, thus rendering chemotherapy ineffective. To overcome this obstacle, two strategies - targeting transporter regulation and direct transporter inhibition - have been proposed. In this review, we focus on these strategies. We first introduce the latest findings on signaling pathways that could potentially be targeted to down-regulate P-gp and BCRP expression and/or transport activity. We then highlight in detail the new paradigm of P-gp and BCRP working as a “cooperative team of gatekeepers” at the blood-brain barrier, discuss its ramifications for brain cancer therapy, and summarize the latest findings on dual P-gp/BCRP inhibitors. Finally, we provide a brief summary with conclusions and outline the perspectives for future research endeavors in this field.
Keywords: BCRP, P-gp, brain cancer, glioblastoma, multidrug resistance, blood-brain barrier, regulation, inhibition, anti-cancer drugs, Chemotherapeutics
Current Pharmaceutical Design
Title: Breast Cancer Resistance Protein and P-Glycoprotein in Brain Cancer: Two Gatekeepers Team Up
Volume: 17 Issue: 26
Author(s): Sagar Agarwal, Anika M.S. Hartz, William F. Elmquist and Bjorn Bauer
Affiliation:
Keywords: BCRP, P-gp, brain cancer, glioblastoma, multidrug resistance, blood-brain barrier, regulation, inhibition, anti-cancer drugs, Chemotherapeutics
Abstract: Brain cancer is a devastating disease. Despite extensive research, treatment of brain tumors has been largely ineffective and the diagnosis of brain cancer remains uniformly fatal. Failure of brain cancer treatment may be in part due to limitations in drug delivery, influenced by the ABC drug efflux transporters P-gp and BCRP at the blood-brain and blood-tumor barriers, in brain tumor cells, as well as in brain tumor stem-like cells. P-gp and BCRP limit various anti-cancer drugs from entering the brain and tumor tissues, thus rendering chemotherapy ineffective. To overcome this obstacle, two strategies - targeting transporter regulation and direct transporter inhibition - have been proposed. In this review, we focus on these strategies. We first introduce the latest findings on signaling pathways that could potentially be targeted to down-regulate P-gp and BCRP expression and/or transport activity. We then highlight in detail the new paradigm of P-gp and BCRP working as a “cooperative team of gatekeepers” at the blood-brain barrier, discuss its ramifications for brain cancer therapy, and summarize the latest findings on dual P-gp/BCRP inhibitors. Finally, we provide a brief summary with conclusions and outline the perspectives for future research endeavors in this field.
Export Options
About this article
Cite this article as:
Agarwal Sagar, M.S. Hartz Anika, F. Elmquist William and Bauer Bjorn, Breast Cancer Resistance Protein and P-Glycoprotein in Brain Cancer: Two Gatekeepers Team Up, Current Pharmaceutical Design 2011; 17 (26) . https://dx.doi.org/10.2174/138161211797440186
DOI https://dx.doi.org/10.2174/138161211797440186 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
The Synergistic Effects of DNA-Targeted Chemotherapeutics and Histone Deacetylase Inhibitors As Therapeutic Strategies for Cancer Treatment
Current Medicinal Chemistry Engineered Nanoparticles in Cancer Therapy
Recent Patents on Drug Delivery & Formulation Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors from the Natural Origin: A Recent Perspective
Anti-Cancer Agents in Medicinal Chemistry Wnt/β-Catenin/LEF-1 Signaling in Chronic Lymphocytic Leukemia (CLL): A Target for Current and Potential Therapeutic Options
Current Cancer Drug Targets Fluorescent Molecular Imaging: Technical Progress and Current Preclinical and Clinical Applications in Urogynecologic Diseases
Current Molecular Medicine Autoimmune Channelopathies of the Nervous System
Current Neuropharmacology Alzheimers Disease - An Interactive Perspective
Current Alzheimer Research Synthesis, Biological Evaluation and Molecular Docking Studies Against EGFR Tyrosine Kinase of 3,5-bis(substituted benzylidene)-1- ethylpiperidin-4-one Analogues
Letters in Organic Chemistry Chemical Modifications of Ketoprofen (NSAID) in Search of Better Lead Compounds: A Review of Literature From 2004-2016
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Therapeutic Targeting of Chemokines with Monoclonal Antibodies
Current Immunology Reviews (Discontinued) Syntheses and Biological Activities of triazole-based Sulfonamides
Current Organic Chemistry Current Progresses in Metal-based Anticancer Complexes as Mammalian TrxR Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Optimization of Drug Safety Profile in Inflammatory Bowel Disease Through a Personalized Approach
Current Drug Targets Plant Natural Products in Anticancer Drug Discovery
Current Organic Chemistry Differential Gene Expression of BRCA1, ERBB2 and TP53 Biomarkers between Human Breast Tissue and Peripheral Blood Samples of Breast Cancer Patients
Anti-Cancer Agents in Medicinal Chemistry Targeting the Endocannabinoid System for the Treatment of Cancer – A Practical View
Current Topics in Medicinal Chemistry Smoking, Estradiol Metabolism and Hormone Replacement Therapy
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Regulation of the Metabolism of Polyunsaturated Fatty Acids and Butyrate in Colon Cancer Cells
Current Pharmaceutical Biotechnology Histone Deacetylase Inhibitors: Molecular and Biological Activity as a Premise to Clinical Application
Current Drug Metabolism Angiogenesis-Related Proteins - Their Role in the Pathogenesis and Treatment of Inflammatory Bowel Disease
Current Protein & Peptide Science