Abstract
The success of anticancer therapy is limited due to the resistance caused by tumor cells to cytotoxic agents, which interfere with the effectiveness of various chemotherapeutic agents. Several mechanisms for decreased effectiveness of anti-cancer drugs have been examined however the most widely studied mechanism is the efflux of cytotoxic drugs from the cell due to P-gp overexpression. However, the role of P-gp inhibitors in improving chemotherapy is limited due to the existence of other mechanisms of resistance such as activation of glutathione mediated detoxification, blockade of DNA repair, apoptotic pathways, TK signaling pathways and altered tumor microenvironment. Alternative strategies to overcome factors responsible for reduced efficacy of cancer therapy have also been considered such as inhibition of the detoxification system like glutathione, targeting Tks and DNA repair pathways, combination of angiogenic inhibitors, RNAi mediated inhibition of targeted genes etc. Additionally, preventing the onset of resistance can be targeted via siRNA strategy and nanoparticle strategy. In this review, we describe detailed mechanisms involved in decreasing effectiveness of anticancer drugs as well as the strategies used to modulate these mechanisms for effective cancer treatment.
Keywords: Angiogenesis, apoptotic pathways, cancer, DNA repair pathways, inhibitors, multidrug resistance, nanoparticle strategy, RNAi strategy, tyrosine kinases inhibitors.
Anti-Cancer Agents in Medicinal Chemistry
Title:Physiological Modulation Approaches to Improve Cancer Chemotherapy : A Review
Volume: 14 Issue: 5
Author(s): Rajesh Kumar, Maninder Kaur and Om Silakari
Affiliation:
Keywords: Angiogenesis, apoptotic pathways, cancer, DNA repair pathways, inhibitors, multidrug resistance, nanoparticle strategy, RNAi strategy, tyrosine kinases inhibitors.
Abstract: The success of anticancer therapy is limited due to the resistance caused by tumor cells to cytotoxic agents, which interfere with the effectiveness of various chemotherapeutic agents. Several mechanisms for decreased effectiveness of anti-cancer drugs have been examined however the most widely studied mechanism is the efflux of cytotoxic drugs from the cell due to P-gp overexpression. However, the role of P-gp inhibitors in improving chemotherapy is limited due to the existence of other mechanisms of resistance such as activation of glutathione mediated detoxification, blockade of DNA repair, apoptotic pathways, TK signaling pathways and altered tumor microenvironment. Alternative strategies to overcome factors responsible for reduced efficacy of cancer therapy have also been considered such as inhibition of the detoxification system like glutathione, targeting Tks and DNA repair pathways, combination of angiogenic inhibitors, RNAi mediated inhibition of targeted genes etc. Additionally, preventing the onset of resistance can be targeted via siRNA strategy and nanoparticle strategy. In this review, we describe detailed mechanisms involved in decreasing effectiveness of anticancer drugs as well as the strategies used to modulate these mechanisms for effective cancer treatment.
Export Options
About this article
Cite this article as:
Kumar Rajesh, Kaur Maninder and Silakari Om, Physiological Modulation Approaches to Improve Cancer Chemotherapy : A Review, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (5) . https://dx.doi.org/10.2174/18715206113136660364
DOI https://dx.doi.org/10.2174/18715206113136660364 |
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
-
Algorithms and Criteria for Transcatheter Aortic Valve Replacement Patient Selection: Current Status and Future Trends
Current Pharmaceutical Design ACKNOWLEDGEMENTS TO REVIEWERS
Clinical Cancer Drugs Is the Vagina an Adequate Route for the Administration of Hormonal Contraceptives?
Current Drug Metabolism Solid Phase Synthesis of Oxytocin Analogues Conjugated to Polyamino Polycarboxylic Ligands
Letters in Organic Chemistry Role of the Hypoxic Microenvironment in the Antitumor Activity of Tyrosine Kinase Inhibitors
Current Medicinal Chemistry Role of Farletuzumab in Epithelial Ovarian Carcinoma
Current Pharmaceutical Design Magnetic Resonance Imaging Findings of Sixth Cranial Nerve Palsies in Patients Presenting with Diplopia
Current Medical Imaging Star Graphs of Protein Sequences and Proteome Mass Spectra in Cancer Prediction
Current Proteomics Biological Evaluation of Azomethine-dihydroquinazolinone Conjugates as Cancer and Cholinesterase Inhibitors
Medicinal Chemistry MicroRNA Pathways: An Emerging Role in Identification of Therapeutic Strategies
Current Gene Therapy Recent Trends in Targeted Anticancer Prodrug and Conjugate Design
Current Medicinal Chemistry Application of Sterylglucoside-Containing Particles for Drug Delivery
Current Pharmaceutical Biotechnology Excessive Oxidative Stress in the Synergistic Effects of Shikonin on the Hyperthermia-Induced Apoptosis
Current Molecular Medicine A Combination of 3D-QSAR Modeling and Molecular Docking Approach for the Discovery of Potential HIF Prolyl Hydroxylase Inhibitors
Medicinal Chemistry Synthetic Approaches to the 2006 New Drugs
Mini-Reviews in Medicinal Chemistry Urine-derived Stem Cells, A New Source of Seed Cells for Tissue Engineering
Current Stem Cell Research & Therapy Meet Our Editorial Board Member
Anti-Cancer Agents in Medicinal Chemistry Structure of Cytochrome P450s and Personalized Drug
Current Medicinal Chemistry Synthesis and Anti-Oxidant Evaluation of Some Novel Sulfa Drugs
Letters in Drug Design & Discovery Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole
Current Drug Metabolism