Abstract
Cancer cells alter their metabolism to support the uninterrupted supply of biosynthetic molecules required for continuous proliferation. Glucose metabolism is frequently reprogrammed in several tumors in addition to fatty acid, amino acid and glutamine metabolism. Pyruvate Dehydrogenase Kinase (PDK) is a gatekeeper enzyme involved in altered glucose metabolism in tumors. There are four isoforms of PDK (1 to 4) in humans. PDK phosphorylates E1α subunit of pyruvate dehydrogenase complex (PDC) and inactivates it. PDC decarboxylates pyruvate to acetyl CoA, which is further metabolized in mitochondria. Overexpression of PDK was observed in several tumors and is frequently associated with chemotherapy related drug resistance, invasion and metastasis. Elevated expression of PDK leads to a shift in glucose metabolism towards glycolysis instead of oxidative phosphorylation. This review summarizes recent literature related to the role of PDKs in cancer and their inhibition as a strategy. In particular, we discuss the role of PDK in tumor progression, metabolic reprogramming in stem cells, and their regulation by miRNAs and lncRNAs, oncogenes and tumor suppressors. Further, we review strategies aimed at targeting PDK to halt tumor growth and progression.
Keywords: Pyruvate dehydrogenase kinase (PDK), cancer, glucose metabolism, PDK regulation, cancer stemness, therapy related resistance, PDK inhibition.
Current Topics in Medicinal Chemistry
Title:Inhibition of Pyruvate Dehydrogenase Kinase as a Therapeutic Strategy against Cancer
Volume: 18 Issue: 6
Author(s): Swatishree Sradhanjali and Mamatha M. Reddy*
Affiliation:
- The Operation Eyesight Universal Institute for Eye Cancer, L V Prasad Eye Institute, Bhubaneswar,India
Keywords: Pyruvate dehydrogenase kinase (PDK), cancer, glucose metabolism, PDK regulation, cancer stemness, therapy related resistance, PDK inhibition.
Abstract: Cancer cells alter their metabolism to support the uninterrupted supply of biosynthetic molecules required for continuous proliferation. Glucose metabolism is frequently reprogrammed in several tumors in addition to fatty acid, amino acid and glutamine metabolism. Pyruvate Dehydrogenase Kinase (PDK) is a gatekeeper enzyme involved in altered glucose metabolism in tumors. There are four isoforms of PDK (1 to 4) in humans. PDK phosphorylates E1α subunit of pyruvate dehydrogenase complex (PDC) and inactivates it. PDC decarboxylates pyruvate to acetyl CoA, which is further metabolized in mitochondria. Overexpression of PDK was observed in several tumors and is frequently associated with chemotherapy related drug resistance, invasion and metastasis. Elevated expression of PDK leads to a shift in glucose metabolism towards glycolysis instead of oxidative phosphorylation. This review summarizes recent literature related to the role of PDKs in cancer and their inhibition as a strategy. In particular, we discuss the role of PDK in tumor progression, metabolic reprogramming in stem cells, and their regulation by miRNAs and lncRNAs, oncogenes and tumor suppressors. Further, we review strategies aimed at targeting PDK to halt tumor growth and progression.
Export Options
About this article
Cite this article as:
Sradhanjali Swatishree and Reddy M. Mamatha*, Inhibition of Pyruvate Dehydrogenase Kinase as a Therapeutic Strategy against Cancer, Current Topics in Medicinal Chemistry 2018; 18 (6) . https://dx.doi.org/10.2174/1568026618666180523105756
DOI https://dx.doi.org/10.2174/1568026618666180523105756 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
- Announcements
Related Articles
-
Intravitreal Anti-VEGF Drugs as Adjuvant Therapy in Diabetic Retinopathy Surgery
Current Diabetes Reviews Primary and Secondary Hypertriglyceridaemia
Current Drug Targets Recent Patents in X-Ray Phase Contrast Imaging
Recent Patents on Biomedical Engineering (Discontinued) Dosage Form Developments of Nanosuspension Drug Delivery System for Oral Administration Route
Current Pharmaceutical Design Telomeres and Thyroid Cancer
Current Genomics Covid-19 Susceptibility and Severity Might be Modified by Vitamin D Status: Theoretical and Practical Considerations
Current Respiratory Medicine Reviews Editorial: The Importance of Case Reports and Case Series in Helping Diagnose Rare Diseases
Current Respiratory Medicine Reviews Cell Clocks and Neuronal Networks: Neuron Ticking and Synchronization in Aging and Aging-Related Neurodegenerative Disease
Current Alzheimer Research Congenital Malformations Attributed to Prenatal Exposure to Cyclophosphamide
Anti-Cancer Agents in Medicinal Chemistry Recent Patents on the Baculovirus Systems
Recent Patents on Biotechnology Advances in the Management of Brain Tumors in Infants
Current Cancer Therapy Reviews Medullary Thyroid Cancer: A Promising Model for Targeted Therapy
Current Molecular Medicine Heterocycles in the Treatment of Neglected Tropical Diseases
Current Medicinal Chemistry The Role of Mediterranean Diet, CoQ10 and Conjugated-Melatonin in Osteoporosis Primary Prevention and Therapy
Current Nutrition & Food Science Biomedical Applications of Poly(Lactic Acid)
Recent Patents on Regenerative Medicine Revolutionary Impact of Nanodrug Delivery on Neuroscience
Current Neuropharmacology Cardiovascular Complications of Sleep Disorders: A Better Night’s Sleep for a Healthier Heart / From Bench to Bedside
Current Vascular Pharmacology Photo- and Sono-Dynamic Therapy: A Review of Mechanisms and Considerations for Pharmacological Agents Used in Therapy Incorporating Light and Sound
Current Pharmaceutical Design Mitochondrial Functionality and Chemical Compound Action on Sperm Function
Current Medicinal Chemistry Pulmonary and Nasal Anti-Inflammatory and Anti-Allergy Inhalation Aerosol Delivery Systems
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry