Abstract
Pancreatic ductal adenocarcinoma (PDAC) is quite resistant to conventional treatments, and gemcitabine, the standard chemotherapeutic agent, offers only a small benefit. Development and progression of PDAC are complex processes involving dysregulation of multiple signal transduction pathways arising from not only genetic but also epigenetic alterations. This makes the epigenetic approach to the treatment of PDAC of great interest. Histone deacetylases, a family of enzymes that, by removal of acetyl groups from a variety of histone and nonhistone proteins, play an important role in the epigenetic regulation of gene expression, are frequently dysregulated in PDAC. In particular, overexpression of class I histone deacetylases has been related to higher tumor grade, poor prognosis and development of chemoresistance. Histone deacetylase inhibitors (HDACIs), a novel class of agents endowed with pleiotropic antitumor effects, appear promising either for their preferential toxicity towards transformed as compared to normal cells and their ability to synergistically enhance the anticancer activity of radiotherapy and many chemotherapeutic agents. Many HDACIs have been shown to increase the antiproliferative and proapoptotic effects of gemcitabine, 5-fluorouracil and bortezomib, a new proteasome inhibitor, in vitro and in vivo PDAC xenograft models. MGCD0103, romidepsin, panobinostat, vorinostat and valproic acid, are currently being tested in association with radiotherapy or chemotherapy (gemcitabine, fluoropyrimidines, proteasome inhibitors) in phase I-II clinical trials in patients with locally advanced or metastatic PDAC.
Keywords: Cancer therapy, epigenetic, histone deacetylase, histone deacetylase inhibitor, molecular targeted therapy, pancreatic ductal adenocarcinoma, HDACs IN PDAC, 10-epoxy-decanoyl, gemcitabine, interleukin-13 Receptor 2, non-homologous end-joining, reactive oxygen species, radiation therapy
Current Cancer Drug Targets
Title:An Epigenetic Approach to Pancreatic Cancer Treatment: The Prospective Role of Histone Deacetylase Inhibitors
Volume: 12 Issue: 4
Author(s): Nicola Tinari, Michele De Tursi, Antonino Grassadonia, Marinella Zilli, Liborio Stuppia, Stefano Iacobelli and Clara Natoli
Affiliation:
Keywords: Cancer therapy, epigenetic, histone deacetylase, histone deacetylase inhibitor, molecular targeted therapy, pancreatic ductal adenocarcinoma, HDACs IN PDAC, 10-epoxy-decanoyl, gemcitabine, interleukin-13 Receptor 2, non-homologous end-joining, reactive oxygen species, radiation therapy
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is quite resistant to conventional treatments, and gemcitabine, the standard chemotherapeutic agent, offers only a small benefit. Development and progression of PDAC are complex processes involving dysregulation of multiple signal transduction pathways arising from not only genetic but also epigenetic alterations. This makes the epigenetic approach to the treatment of PDAC of great interest. Histone deacetylases, a family of enzymes that, by removal of acetyl groups from a variety of histone and nonhistone proteins, play an important role in the epigenetic regulation of gene expression, are frequently dysregulated in PDAC. In particular, overexpression of class I histone deacetylases has been related to higher tumor grade, poor prognosis and development of chemoresistance. Histone deacetylase inhibitors (HDACIs), a novel class of agents endowed with pleiotropic antitumor effects, appear promising either for their preferential toxicity towards transformed as compared to normal cells and their ability to synergistically enhance the anticancer activity of radiotherapy and many chemotherapeutic agents. Many HDACIs have been shown to increase the antiproliferative and proapoptotic effects of gemcitabine, 5-fluorouracil and bortezomib, a new proteasome inhibitor, in vitro and in vivo PDAC xenograft models. MGCD0103, romidepsin, panobinostat, vorinostat and valproic acid, are currently being tested in association with radiotherapy or chemotherapy (gemcitabine, fluoropyrimidines, proteasome inhibitors) in phase I-II clinical trials in patients with locally advanced or metastatic PDAC.
Export Options
About this article
Cite this article as:
Tinari Nicola, De Tursi Michele, Grassadonia Antonino, Zilli Marinella, Stuppia Liborio, Iacobelli Stefano and Natoli Clara, An Epigenetic Approach to Pancreatic Cancer Treatment: The Prospective Role of Histone Deacetylase Inhibitors, Current Cancer Drug Targets 2012; 12 (4) . https://dx.doi.org/10.2174/156800912800190884
DOI https://dx.doi.org/10.2174/156800912800190884 |
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
-
Incorporating Link Information in Feature Selection for Identifying Tumor Biomarkers by Using miRNA-mRNA Paired Expression Data
Current Proteomics Synthesis and Evaluation of New Thiazolyl Hydrazone Derivatives as Potential Anticancer Agents
Letters in Drug Design & Discovery Multiple VEGF Family Members are Simultaneously Expressed in Ovarian Cancer: a Proposed Model for Bevacizumab Resistance
Current Pharmaceutical Design Glioblastoma: Prognostic Factors and Predictive Response to Radio and Chemotherapy
Current Medicinal Chemistry Mitocans: Mitochondrial Targeted Anti-Cancer Drugs as Improved Therapies and Related Patent Documents
Recent Patents on Anti-Cancer Drug Discovery β-Lactams as Neuroprotective Agents
Anti-Infective Agents in Medicinal Chemistry Activation of Human Platelets by 2-Arachidonoylglycerol: Role of PKC in NO/cGMP Pathway Modulation
Current Neurovascular Research Modulating the Hypoxia-Inducible Factor Signaling Pathway: Applications From Cardiovascular Disease to Cancer
Current Pharmaceutical Design In vivo Near-infrared Fluorescence Tumor Imaging Using DiR-loaded Nanocarriers
Current Drug Delivery Updates of mTOR Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Development of 96-microwell Plate Assay with Fluorescence Reader and HPLC Method with Fluorescence Detection for High-throughput Analysis of Linifanib in its Bulk and Dosage Forms
Current Pharmaceutical Analysis Xanthones as Potential Antioxidants
Current Medicinal Chemistry Cancer and Stem Cells
Current Cancer Therapy Reviews TGF-Beta Type I Receptor (Alk5) Kinase Inhibitors in Oncology
Current Pharmaceutical Biotechnology In silico Modeling Studies of 5-HT2B Antagonistic Activity of 2-(2- phenylethyl)chromone Derivatives from Cucumis melo Seeds
Letters in Drug Design & Discovery Advancing the Therapeutic Efficacy of Bioactive Molecules by Delivery Vehicle Platforms
Current Medicinal Chemistry Preventive and Protective Roles of Dietary Nrf2 Activators Against Central Nervous System Diseases
CNS & Neurological Disorders - Drug Targets Recent Trends of Biocompatible and Biodegradable Nanoparticles in Drug Delivery: A Review
Current Medicinal Chemistry Meet Our Editorial Board Member
Current Cancer Therapy Reviews Basic Mechanisms Involved in the Anti-Cancer Effects of Melatonin
Current Medicinal Chemistry