Abstract
The recent discoveries of genomic and molecular markers in hepatocellular carcinoma (HCC) have improved the understanding about the complexity of the signal transduction pathways as well as their relevance in normal and liver cancer cells. The identification of the functional repercussions of punctual mutations and crosstalk among cell signaling will promote the identification of specific combinatorial targeted molecular therapies to specific subsets of patients which will allow the development of personalized-based therapy and increase the survival of patients.
Numerous molecular targets are in the cross-road between oncogenic and anti-apoptotic programs, genetic or epigenetic alterations, which overall may have a similar cellular phenotype. The standard antineoplastic chemotherapeutic regimes based on cytotoxic agents leads to significant side effect and modest response rates, marginal changes in natural history, and toxicities that may impact the quality of life of patients. Different strategies involving gene therapy, targeted antibodies or small molecules have been used to regulate cell death/proliferation signals, as well as angiogenesis in liver tumors. In this sense, Sorafenib recently approved for renal cell carcinoma, represents the first tyrosine kinase inhibitor (TKI) licensed for the treatment of patients with advanced HCC. This review summarizes the current status of molecular receptor TKI-based targeted therapy in HCC driving different pathways involved in cell survival, proliferation, migration, angiogenesis and metastasis, which include the regulation of Raf/MEK/ERK, PI3K/Akt/mTOR, and Jak/STAT cell signaling. The study also provides information about cell signaling crosstalk relevant in tyrosine kinase receptors (TKR)-based systemic therapy in HCC.
Keywords: Cancer, cell death, proliferation, receptors, tumor
Current Cancer Drug Targets
Title:Targeting Tyrosine Kinase Receptors in Hepatocellular Carcinoma
Volume: 13 Issue: 3
Author(s): Jordi Muntane, Angel J. De la Rosa, Fernando Docobo, Rocio Garcia-Carbonero and Francisco J. Padillo
Affiliation:
Keywords: Cancer, cell death, proliferation, receptors, tumor
Abstract: The recent discoveries of genomic and molecular markers in hepatocellular carcinoma (HCC) have improved the understanding about the complexity of the signal transduction pathways as well as their relevance in normal and liver cancer cells. The identification of the functional repercussions of punctual mutations and crosstalk among cell signaling will promote the identification of specific combinatorial targeted molecular therapies to specific subsets of patients which will allow the development of personalized-based therapy and increase the survival of patients.
Numerous molecular targets are in the cross-road between oncogenic and anti-apoptotic programs, genetic or epigenetic alterations, which overall may have a similar cellular phenotype. The standard antineoplastic chemotherapeutic regimes based on cytotoxic agents leads to significant side effect and modest response rates, marginal changes in natural history, and toxicities that may impact the quality of life of patients. Different strategies involving gene therapy, targeted antibodies or small molecules have been used to regulate cell death/proliferation signals, as well as angiogenesis in liver tumors. In this sense, Sorafenib recently approved for renal cell carcinoma, represents the first tyrosine kinase inhibitor (TKI) licensed for the treatment of patients with advanced HCC. This review summarizes the current status of molecular receptor TKI-based targeted therapy in HCC driving different pathways involved in cell survival, proliferation, migration, angiogenesis and metastasis, which include the regulation of Raf/MEK/ERK, PI3K/Akt/mTOR, and Jak/STAT cell signaling. The study also provides information about cell signaling crosstalk relevant in tyrosine kinase receptors (TKR)-based systemic therapy in HCC.
Export Options
About this article
Cite this article as:
Muntane Jordi, J. De la Rosa Angel, Docobo Fernando, Garcia-Carbonero Rocio and J. Padillo Francisco, Targeting Tyrosine Kinase Receptors in Hepatocellular Carcinoma, Current Cancer Drug Targets 2013; 13 (3) . https://dx.doi.org/10.2174/15680096113139990075
DOI https://dx.doi.org/10.2174/15680096113139990075 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Meta-Analysis of Anticancer Drug Structures - Significance of Their Polar Allylic Moieties
Anti-Cancer Agents in Medicinal Chemistry Peptides Targeting Angiogenesis Related Growth Factor Receptors
Current Pharmaceutical Design Synthesis and Evaluation of Cytotoxic Activity of Some Pyrroles and Fused Pyrroles
Anti-Cancer Agents in Medicinal Chemistry Cadmium-containing Quantum Dots: Current Perspectives on Their Application as Nanomedicine and Toxicity Concerns
Mini-Reviews in Medicinal Chemistry Strategies to Overcome Multi-Drug Resistance in Cancer Cells: the Contribution of siRNA and Nanotechnologies
Current Organic Chemistry Role of Tumor Microenvironment in Cancer Stem Cells Resistance to Radiotherapy
Current Cancer Drug Targets Nonalcoholic Fatty Liver Disease (NAFLD) for Primary Care Providers: Beyond the Liver
Current Hypertension Reviews The Pim Kinases: New Targets for Drug Development
Current Drug Targets Critical Role of Hypoxia Sensor - HIF-1α in VEGF Gene Activation. Implications for Angiogenesis and Tissue Injury Healing
Current Medicinal Chemistry Cyclin-Dependent Kinase Inhibition by Flavoalkaloids
Mini-Reviews in Medicinal Chemistry 2-Deoxy-D-Ribose, a Downstream Mediator of Thymidine Phosphorylase, Regulates Tumor Angiogenesis and Progression
Anti-Cancer Agents in Medicinal Chemistry Multifunctional Materials for Cancer Therapy: From Antitumoral Agents to Innovative Administration
Current Organic Chemistry Exploring Mechanisms of MicroRNA Downregulation in Cancer
MicroRNA Processed Foods, Dysbiosis, Systemic Inflammation, and Poor Health
Current Nutrition & Food Science Diverse Mechanisms of AKT Pathway Activation in Human Malignancy
Current Cancer Drug Targets The Warburg Effect: Why and How Do Cancer Cells Activate Glycolysis in the Presence of Oxygen?
Anti-Cancer Agents in Medicinal Chemistry Neuro-endocrine Markers in Neoplasms. Diagnostic Interest and Future Prospects
Current Proteomics Ring Finger Ubiquitin Protein Ligases and Their Implication to the Pathogenesis of Human Diseases
Current Pharmaceutical Design γ δ T Cell Modulation in Anticancer Treatment
Current Cancer Drug Targets 6-Bromo-2,3-Dioxoindolin Phenylacetamide Derivatives: Synthesis, Potent CDC25B, PTP1B Inhibitors and Anticancer Activity
Letters in Drug Design & Discovery