Abstract
Hepatocellular carcinoma and cholangiocarcinoma are the two most important primary malignancies of the liver. These are among the tumours with the lowest response to pharmacological treatment based on currently available drugs. This is due either to the existence of refractoriness of the initial tumour or to the ability of cancer cells to develop chemoresistance during treatment. Liver cancers share some of the mechanisms responsible for drug refractoriness with other types of tumours, such as a reduction in drug uptake; enhanced drug export; intracellular inactivation of the active agent; alteration of the molecular target; an increase in the activity of the target route to be inhibited, or the appearance or stimulation of alternative routes; enhanced repair of drug-induced modifications in the target molecules, and the activation/ inhibition of intracellular signalling pathways, all of which lead to a negative balance between the apoptosis/survival of tumour cells. The aim of the present article is to review how these mechanisms of chemoresistance affect the different families of drugs that are being or have been used to treat hepatocellular carcinoma and cholangiocarcinoma. A better understanding of the molecular bases of drug refractoriness is needed in order to develop novel drugs or pharmacological strategies aimed at overcoming resistance to anticancer agents.
Keywords: ABC proteins, Anticancer Drugs, Apoptosis, Cholangiocarcinoma, Efflux, Hepatocellular Carcinoma, Survival, Uptake
Current Medicinal Chemistry
Title: Molecular Bases of Liver Cancer Refractoriness to Pharmacological Treatment
Volume: 17 Issue: 8
Author(s): J. J.G. Marin, M. R. Romero and O. Briz
Affiliation:
Keywords: ABC proteins, Anticancer Drugs, Apoptosis, Cholangiocarcinoma, Efflux, Hepatocellular Carcinoma, Survival, Uptake
Abstract: Hepatocellular carcinoma and cholangiocarcinoma are the two most important primary malignancies of the liver. These are among the tumours with the lowest response to pharmacological treatment based on currently available drugs. This is due either to the existence of refractoriness of the initial tumour or to the ability of cancer cells to develop chemoresistance during treatment. Liver cancers share some of the mechanisms responsible for drug refractoriness with other types of tumours, such as a reduction in drug uptake; enhanced drug export; intracellular inactivation of the active agent; alteration of the molecular target; an increase in the activity of the target route to be inhibited, or the appearance or stimulation of alternative routes; enhanced repair of drug-induced modifications in the target molecules, and the activation/ inhibition of intracellular signalling pathways, all of which lead to a negative balance between the apoptosis/survival of tumour cells. The aim of the present article is to review how these mechanisms of chemoresistance affect the different families of drugs that are being or have been used to treat hepatocellular carcinoma and cholangiocarcinoma. A better understanding of the molecular bases of drug refractoriness is needed in order to develop novel drugs or pharmacological strategies aimed at overcoming resistance to anticancer agents.
Export Options
About this article
Cite this article as:
Marin J.G. J., Romero R. M. and Briz O., Molecular Bases of Liver Cancer Refractoriness to Pharmacological Treatment, Current Medicinal Chemistry 2010; 17 (8) . https://dx.doi.org/10.2174/092986710790514462
DOI https://dx.doi.org/10.2174/092986710790514462 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Bile Acids as Novel Pharmacological Agents: The Interplay Between Gene Polymorphisms, Epigenetic Factors and Drug Response
Current Pharmaceutical Design Main Nutritional and Environmental Risk Factors in Children with Leukemia from a Public Hospital of the State of Guanajuato, Mexico
Current Cancer Therapy Reviews Discovery and Development of Topoisomerase Inhibitors as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Viral Product Trafficking to Mitochondria, Mechanisms and Roles in Pathogenesis
Infectious Disorders - Drug Targets Relevance of Multidrug Resistance Proteins on the Clinical Efficacy of Cancer Therapy
Current Drug Delivery Ribonucleotide Reductase: A Mechanistic Portrait of Substrate Analogues Inhibitors
Current Medicinal Chemistry New and Highly Potent Antitumor Natural Products from Marine-Derived Fungi: Covering the Period from 2003 to 2012
Current Topics in Medicinal Chemistry Experimental Strategies in Autoimmunity: Antagonists of Cytokines and their Receptors, Nanocarriers, Inhibitors of Immunoproteasome, Leukocyte Migration and Protein Kinases
Current Pharmaceutical Design Polymeric Nanocarriers: New Endeavors for the Optimization of the Technological Aspects of Drugs
Recent Patents on Biomedical Engineering (Discontinued) SALL4: Engine of Cell Stemness
Current Gene Therapy Resistance Mutations Against HCV Protease Inhibitors and Antiviral Drug Design
Current Pharmaceutical Design Peptide Vaccines for Cancer Therapy
Recent Patents on Inflammation & Allergy Drug Discovery Conventional Anticancer Therapeutics and Telomere Maintenance Mechanisms
Current Pharmaceutical Design Targeting DNA Minor Groove by Hybrid Molecules as Anticancer Agents
Current Medicinal Chemistry Tyrosine Kinase Inhibitors, Pancreatic Hyperenzymemia and Acute Pancreatitis: A Review
Recent Patents on Inflammation & Allergy Drug Discovery A Retrospective Study on <i>Gloriosa superba</i> and Its Main Active Constituents
The Natural Products Journal Histone Lysine-Specific Methyltransferases and Demethylases in Carcinogenesis: New Targets for Cancer Therapy and Prevention
Current Cancer Drug Targets TGF-Beta Inihibitor-loaded Polyelectrolyte Multilayers Capsules for Sustained Targeting of Hepatocarcinoma Cells
Current Pharmaceutical Design Doxycycline in Mitochondrial Mediated Pathway of Apoptosis: A Systematic Review
Anti-Cancer Agents in Medicinal Chemistry Inhibitors of HDACs - Effective Drugs Against Cancer?
Current Cancer Drug Targets