Abstract
Hepatocellular carcinoma (HCC) is a global health problem and responsible for up to 500.000 deaths annually. It usually occurs secondary to infections with hepatitis B or C viruses, alcohol consumption, non-alcoholic steatohepatitis or hereditary liver diseases. The prognosis for patients with advanced disease is dismal; therefore, new strategies to prevent or treat this malignancy are urgently needed. Over recent years, several molecular pathways have been identified contributing to the molecular pathogenesis of this devastating disease, among them the PI3K/AKT/mTOR pathway. mTOR is effectively inhibited by rapamycin and its derivatives such as temsirolimus and everolimus. The anti-tumor activity of rapamycin was identified more than 30 years ago in a screen performed at the National Cancer Institute, but was subsequently not developed for cancer treatment. In the 1990s, activation of the mTOR pathway was recognized in various malignancies spurring again the interest in mTOR inhibitors for anti-cancer treatment. In 2007, the US Food and Drug Administration approved the first mTOR inhibitor, temsirolimus, for the treatment of renal cell carcinoma. Currently, several clinical studies are underway to define the role of mTOR inhibitors for the treatment of hepatocellular carcinoma. The aim of this review is to outline the role of mTOR for hepatocarcinogenesis. We will also discuss the latest preclinical and clinical data of mTOR inhibitors for the prevention and treatment of HCC.
Keywords: Hepatocellular Carcinoma, mTOR, rapamycin, RAD001, Eukaryotic Translation Initiation Factor 4E- Binding Protein 1, Fumarylacetoacetate, Fumarylacetoacetate Hydrolase, Hepatitis B Virus, Hepatitis C Virus, Hypoxia-Inducible Factor-1, Hereditary Tyrosinemia type 1, Mammalian Target of Rapamycin, mTOR Complex 1, Phosphoinositide-3 Kinase, Vascular Endothelial Growth Factor
Current Cancer Drug Targets
Title:mTOR as a Potential Target for the Prevention and Treatment of Hepatocellular Carcinoma
Volume: 12 Issue: 9
Author(s): Laura Elisa Buitrago-Molina and Arndt Vogel
Affiliation:
Keywords: Hepatocellular Carcinoma, mTOR, rapamycin, RAD001, Eukaryotic Translation Initiation Factor 4E- Binding Protein 1, Fumarylacetoacetate, Fumarylacetoacetate Hydrolase, Hepatitis B Virus, Hepatitis C Virus, Hypoxia-Inducible Factor-1, Hereditary Tyrosinemia type 1, Mammalian Target of Rapamycin, mTOR Complex 1, Phosphoinositide-3 Kinase, Vascular Endothelial Growth Factor
Abstract: Hepatocellular carcinoma (HCC) is a global health problem and responsible for up to 500.000 deaths annually. It usually occurs secondary to infections with hepatitis B or C viruses, alcohol consumption, non-alcoholic steatohepatitis or hereditary liver diseases. The prognosis for patients with advanced disease is dismal; therefore, new strategies to prevent or treat this malignancy are urgently needed. Over recent years, several molecular pathways have been identified contributing to the molecular pathogenesis of this devastating disease, among them the PI3K/AKT/mTOR pathway. mTOR is effectively inhibited by rapamycin and its derivatives such as temsirolimus and everolimus. The anti-tumor activity of rapamycin was identified more than 30 years ago in a screen performed at the National Cancer Institute, but was subsequently not developed for cancer treatment. In the 1990s, activation of the mTOR pathway was recognized in various malignancies spurring again the interest in mTOR inhibitors for anti-cancer treatment. In 2007, the US Food and Drug Administration approved the first mTOR inhibitor, temsirolimus, for the treatment of renal cell carcinoma. Currently, several clinical studies are underway to define the role of mTOR inhibitors for the treatment of hepatocellular carcinoma. The aim of this review is to outline the role of mTOR for hepatocarcinogenesis. We will also discuss the latest preclinical and clinical data of mTOR inhibitors for the prevention and treatment of HCC.
Export Options
About this article
Cite this article as:
Elisa Buitrago-Molina Laura and Vogel Arndt, mTOR as a Potential Target for the Prevention and Treatment of Hepatocellular Carcinoma, Current Cancer Drug Targets 2012; 12 (9) . https://dx.doi.org/10.2174/15680096112091045
DOI https://dx.doi.org/10.2174/15680096112091045 |
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
-
The Role of Lymphotoxin Receptor Signaling in Diseases
Current Molecular Medicine Biomarkers of Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD), A Review of Published Patents and Patent Applications
Recent Patents on Biomarkers Mesenchymal Stem Cells: An Emerging Tool for Cancer Targeting and Therapy
Current Stem Cell Research & Therapy Cosignaling Molecules Around LIGHT-HVEM-BTLA: From Immune Activation to Therapeutic Targeting
Current Molecular Medicine Lipid Microparticles for Oral Bioavailability Enhancement
Recent Patents on Nanomedicine Emerging Role of Colloidal Drug Delivery Systems (CDDS) in NSAID Topical Administration
Current Medicinal Chemistry Extra-Hepatic Isozymes from the CYP1 and CYP2 Families as Potential Chemotherapeutic Targets
Current Topics in Medicinal Chemistry Synthesis of Xanthones and Benzophenones as Inhibitors of Tumor Cell Growth
Letters in Drug Design & Discovery Prostate Cancer, miRNAs, Metallothioneins and Resistance to Cytostatic Drugs
Current Medicinal Chemistry Copper Complexes of 8-Aminoquinoline and Uracils as Novel Aromatase Inhibitors
Letters in Drug Design & Discovery An Evidence-Based Review of the Mechanism of Action, Efficacy, and Safety of Biologic Therapies in the Treatment of Psoriasis and Psoriatic Arthritis
Current Medicinal Chemistry Molecular Dynamics and Structural Studies of the Ets Domain-DNA Complexes
Current Bioinformatics Cancer Therapy-Induced Residual Bone Marrow Injury: Mechanisms of Induction and Implication for Therapy
Current Cancer Therapy Reviews Hot topic: Editorial [Therapeutic Potential of Peptide Motifs - Part IV] (Jean Claude Herve)
Current Pharmaceutical Design Immune Responses to Gene-Modified T Cells
Current Gene Therapy Phytochemicals - A Novel and Prominent Source of Anti-cancer Drugs Against Colorectal Cancer
Combinatorial Chemistry & High Throughput Screening Role of NUCB2/nesfatin-1 as a Possible Biomarker
Current Pharmaceutical Design Recent Advancements in Diagnosis and Therapy of Liver Cirrhosis
Current Drug Targets Treatment of Insomnia, Insomnia Symptoms, and Obstructive Sleep Apnea During and After Menopause: Therapeutic Approaches
Current Psychiatry Reviews Meet Our Associate Editorial Board Member
Current Pharmaceutical Biotechnology