Abstract
Histone deacetylase inhibitors (HDACi) have been demonstrated as an emerging class of anticancer drugs involved in regulation of gene expression and chromatin remodeling thus indicating valid targets for different types of cancer therapeutics. The pan-deacetylase inhibitor panobinostat (Farydac®, LBH589) is developed by Novartis Pharmaceuticals and a newly US FDA approved drug for the multiple myeloma. It is under clinical investigation for a range of hematological and solid tumors worldwide in both oral and intravenous formulations. Panobinostat inhibits tumor cell growth by interacting with acetylation of histones and nonhistone proteins as well as various apoptotic, autophagy-mediated targets and various tumorigenesis pathways involved in the development of cancer. The current article summarizes the status of panobinostat in gastrointestinal cancers. Preclinical and clinical data suggest that panobinostat has potential inhibitory activity in hepatocellular, pancreatic, colorectal, gastric and gastrointestinal stromal tumors. Clinical evaluations of panobinostat are currently underway. Herein, we have also reviewed the rationale behind the combination therapy under the trials and possible future prospective for the treatment of GI tumors.
Keywords: HDAC, HDACi, panobinostat, combination therapy, GI tumors, preclinical and clinical studies.
Current Cancer Drug Targets
Title:The Safety, Efficacy and Therapeutic Potential of Histone Deacetylase Inhibitors with Special Reference to Panobinostat in Gastrointestinal Tumors: A Review of Preclinical and Clinical Studies
Volume: 18 Issue: 8
Author(s): Avineesh Singh, Preeti Patel, Jageshwar, Vijay Kumar Patel, Deepak Kumar Jain, M. Kamal and Harish Rajak*
Affiliation:
- Medicinal Chemistry Research Laboratory, Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur- 495 009, (C.G.),India
Keywords: HDAC, HDACi, panobinostat, combination therapy, GI tumors, preclinical and clinical studies.
Abstract: Histone deacetylase inhibitors (HDACi) have been demonstrated as an emerging class of anticancer drugs involved in regulation of gene expression and chromatin remodeling thus indicating valid targets for different types of cancer therapeutics. The pan-deacetylase inhibitor panobinostat (Farydac®, LBH589) is developed by Novartis Pharmaceuticals and a newly US FDA approved drug for the multiple myeloma. It is under clinical investigation for a range of hematological and solid tumors worldwide in both oral and intravenous formulations. Panobinostat inhibits tumor cell growth by interacting with acetylation of histones and nonhistone proteins as well as various apoptotic, autophagy-mediated targets and various tumorigenesis pathways involved in the development of cancer. The current article summarizes the status of panobinostat in gastrointestinal cancers. Preclinical and clinical data suggest that panobinostat has potential inhibitory activity in hepatocellular, pancreatic, colorectal, gastric and gastrointestinal stromal tumors. Clinical evaluations of panobinostat are currently underway. Herein, we have also reviewed the rationale behind the combination therapy under the trials and possible future prospective for the treatment of GI tumors.
Export Options
About this article
Cite this article as:
Singh Avineesh , Patel Preeti , Jageshwar , Patel Kumar Vijay, Jain Kumar Deepak, Kamal M. and Rajak Harish*, The Safety, Efficacy and Therapeutic Potential of Histone Deacetylase Inhibitors with Special Reference to Panobinostat in Gastrointestinal Tumors: A Review of Preclinical and Clinical Studies, Current Cancer Drug Targets 2018; 18 (8) . https://dx.doi.org/10.2174/1568009617666170630124643
DOI https://dx.doi.org/10.2174/1568009617666170630124643 |
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
-
2', 4'-dihydroxy-3, 4-methylenedioxychalcone Activate Mitochondrial Apoptosis of Ehrlich Ascites Carcinoma Cells
Current Drug Therapy Regulation and Importance of the PI3K/Akt/mTOR Signaling Pathway in Hematologic Malignancies
Anti-Cancer Agents in Medicinal Chemistry Gallium-68 in Medical Imaging
Current Radiopharmaceuticals Drug-Induced Peripheral Neuropathy: Diagnosis and Management
Current Cancer Drug Targets Phytotherapy and NAFLD - from Goals and Challenges to Clinical Practice
Reviews on Recent Clinical Trials Pharmacological Targeting of the Hsp70 Chaperone
Current Topics in Medicinal Chemistry pH-Sensitive Polymeric Micelles for Programmable Drug and Gene Delivery
Current Pharmaceutical Design Pyrazolo-Triazolo-Pyrimidine Derivatives as Adenosine Receptor Antagonists: A Possible Template for Adenosine Receptor Subtypes?
Current Pharmaceutical Design Recent Advances in Combined Modality Treatment for Locally Advanced Pancreatic Cancer
Current Cancer Therapy Reviews Prediction and Early Evaluation of Anticancer Therapy Response: From Imaging of Drug Efflux Pumps to Targeted Therapy Response
Current Medicinal Chemistry Cyclotron Production of PET Radiometals in Liquid Targets: Aspects and Prospects
Current Radiopharmaceuticals Pharmacokinetic and Pharmacodynamic Variability: A Daunting Challenge in Drug Therapy
Current Drug Metabolism Nanotechnology approaches for pain therapy through transdermal drug delivery
Current Pharmaceutical Design Medicinal Chemistry Approaches of Controlling Gastrointestinal Side Effects of Non-Steroidal Anti-Inflammatory Drugs. Endogenous Protective Mechanisms and Drug Design
Medicinal Chemistry Small-molecule Inhibitors of Fibroblast Growth Factor Receptor (FGFR) Tyrosine Kinases (TK)
Current Pharmaceutical Design Self-assembling Peptide Nanofibers Containing D-amino Acids for Tetrandrine Delivery
Current Signal Transduction Therapy A Structural Insight into Hydroxamic Acid Based Histone Deacetylase Inhibitors for the Presence of Anticancer Activity
Current Medicinal Chemistry Dihydropyrimidine Dehydrogenase Genotyping and Phenotyping for 5- Fluorouracil Dysmetabolism: Moving Towards Personalized Chemotherapy in Patients with Cancer
Current Pharmacogenomics and Personalized Medicine <i>Helicobacter Pylori</i> Interacts with Serum Vitamin D to Influence Hypertension
Current Aging Science Drug Transporters and Multiple Drug Resistance in the Most Common Pediatric Solid Tumors
Current Drug Metabolism