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
-
The Multiple Pharmaceutical Potential of Curcumin in Parkinson's Disease
CNS & Neurological Disorders - Drug Targets MYC as Therapeutic Target for Embryonal Tumors: Potential and Challenges
Current Cancer Drug Targets Insights into a Critical Role of the FOXO3a-FOXM1 Axis in DNA Damage Response and Genotoxic Drug Resistance
Current Drug Targets Nanotechnology, A Tool for Diagnostics and Treatment of Cancer
Current Topics in Medicinal Chemistry The Microarray Gene Profiling Analysis of Glioblastoma Cancer Cells Reveals Genes Affected by FAK Inhibitor Y15 and Combination of Y15 and Temozolomide
Anti-Cancer Agents in Medicinal Chemistry Targeting AMPK Signaling Pathway to Overcome Drug Resistance for Cancer Therapy
Current Drug Targets Stationary Wavelet Transform and AdaBoost with SVM Based Pathological Brain Detection in MRI Scanning
CNS & Neurological Disorders - Drug Targets Preparation, Characterization and Drug Release of Salicylic Acid Loaded Porous Electrospun Nanofibers
Recent Patents on Nanotechnology Therapy Based on the Regulation of Thiol-dependent Redox Systems
Current Medicinal Chemistry Suppression of HIV Replication In Vitro by CpG and CpG Conjugated to the Non Toxic B Subunit of Cholera Toxin
Current HIV Research The Epidermal Growth Factor Receptor as a Therapeutic Target in Glioblastoma Multiforme and other Malignant Neoplasms
Anti-Cancer Agents in Medicinal Chemistry Structure, Function and Inhibition of Bcl-2 Family Proteins: A New Target for Anti-Tumor Agents
Mini-Reviews in Medicinal Chemistry Combination of Anti-EGFR Drugs and Other Molecular Targeted Agents as Anti-Cancer Strategy
Current Cancer Therapy Reviews Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra
Current Genomics In Vitro Modeling of the Blood-Brain Barrier: Simplicity Versus Complexity
Current Pharmaceutical Design Endocannabinoid Signaling in Midbrain Dopamine Neurons: More than Physiology?
Current Neuropharmacology Nose to Brain Delivery: New Trends in Amphiphile-Based “Soft” Nanocarriers
Current Pharmaceutical Design Endothelial Cell Heterogeneity: A Developmental Biologist’s Perspective
Current Angiogenesis (Discontinued) Clinical Update: Treatment of Glioblastoma Multiforme with Radiolabeled Antibodies that Target Tumor Necrosis
Current Cancer Therapy Reviews Integrative Analysis of miRNA-mediated Competing Endogenous RNA Network Reveals the lncRNAs-mRNAs Interaction in Glioblastoma Stem Cell Differentiation
Current Bioinformatics