Abstract
Tumor cells, including leukemic cells, remodel their bioenergetic system in favor of aerobic glycolysis. This process is called “the Warburg effect” and offers an attractive pharmacological target to preferentially eliminate malignant cells. In addition, recent results show that metabolic changes can be linked to tumor immune evasion. Mouse models demonstrate the importance of this metabolic remodeling in leukemogenesis. Some leukemias, although treatable, remain incurable and resistance to chemotherapy produces an elevated percentage of relapse in most leukemia cases. Several groups have targeted the specific metabolism of leukemia cells in preclinical and clinical studies to improve the prognosis of these patients, i.e. using L-asparaginase to treat pediatric acute lymphocytic leukemia (ALL). Additional metabolic drugs that are currently being used to treat other diseases or tumors could also be exploited for leukemia, based on preclinical studies. Finally, we discuss the potential use of several metabolic drugs in combination therapies, including immunomodulatory drugs (IMiDs) or immune cell-based therapies, to increase their efficacy and reduce side effects in the treatment of hematological cancers.
Keywords: Cancer immunosurveillance, DCA, glutamine, metformin, MHC-I, OXPHOS, warburg effect.
Anti-Cancer Agents in Medicinal Chemistry
Title:Chemical Metabolic Inhibitors for the Treatment of Blood-Borne Cancers
Volume: 14 Issue: 2
Author(s): Martin Villalba, Nuria Lopez-Royuela, Ewelina Krzywinska, Moeez G. Rathore, Robert A. Hipskind, Houda Haouas and Nerea Allende-Vega
Affiliation:
Keywords: Cancer immunosurveillance, DCA, glutamine, metformin, MHC-I, OXPHOS, warburg effect.
Abstract: Tumor cells, including leukemic cells, remodel their bioenergetic system in favor of aerobic glycolysis. This process is called “the Warburg effect” and offers an attractive pharmacological target to preferentially eliminate malignant cells. In addition, recent results show that metabolic changes can be linked to tumor immune evasion. Mouse models demonstrate the importance of this metabolic remodeling in leukemogenesis. Some leukemias, although treatable, remain incurable and resistance to chemotherapy produces an elevated percentage of relapse in most leukemia cases. Several groups have targeted the specific metabolism of leukemia cells in preclinical and clinical studies to improve the prognosis of these patients, i.e. using L-asparaginase to treat pediatric acute lymphocytic leukemia (ALL). Additional metabolic drugs that are currently being used to treat other diseases or tumors could also be exploited for leukemia, based on preclinical studies. Finally, we discuss the potential use of several metabolic drugs in combination therapies, including immunomodulatory drugs (IMiDs) or immune cell-based therapies, to increase their efficacy and reduce side effects in the treatment of hematological cancers.
Export Options
About this article
Cite this article as:
Villalba Martin, Lopez-Royuela Nuria, Krzywinska Ewelina, Rathore G. Moeez, Hipskind A. Robert, Haouas Houda and Allende-Vega Nerea, Chemical Metabolic Inhibitors for the Treatment of Blood-Borne Cancers, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (2) . https://dx.doi.org/10.2174/18715206113136660374
DOI https://dx.doi.org/10.2174/18715206113136660374 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
-
Apelin/Apelin Receptor System: Molecular Characteristics, Physiological Roles, and Prospects as a Target for Disease Prevention and Pharmacotherapy
Current Molecular Pharmacology Cyclic Nucleotide Phosphodiesterases (PDE) and Peptide Motifs
Current Pharmaceutical Design Innovative Strategy in Treating Angina Pectoris with Chinese Patent Medicines by Promoting Blood Circulation and Removing Blood Stasis: Experience from Combination Therapy in Chinese Medicine
Current Vascular Pharmacology Ethnopharmacological and Phytopharmaceutical Evaluation of Prosopis cineraria: An Overview and Future Prospects
Current Drug Metabolism Inflammation and Chronic Oxidative Stress in Radiation-Induced Late Normal Tissue Injury: Therapeutic Implications
Current Medicinal Chemistry Prevention and Therapeutic Strategies of Thromboembolic Events in Patients with Inflammatory Bowel Diseases: A Report of Three Cases
Current Drug Targets Aquaretic Agents: Whats Beyond the Treatment of Hyponatremia?
Current Pharmaceutical Design Sex Steroid Hormones, Cardiovascular Diseases and The Metabolic Syndrome
Cardiovascular & Hematological Agents in Medicinal Chemistry Nanoparticulate Drug Delivery Systems for Treatment of Hepatocellular Carcinoma
Current Cancer Therapy Reviews Advances in Peptide Pharmaceuticals
Current Pharmaceutical Biotechnology Current and Future Chemotherapy for Chagas Disease
Current Medicinal Chemistry Kinetic Analysis of Oxime Interactions with Acetylcholinesterase as a Basis for the Evaluation of Oxime Efficacy in Organophosphate Poisoning
Current Bioactive Compounds Nitric Oxide: State of the Art in Drug Design
Current Medicinal Chemistry Platelets as Potential Link Between Diabetes and Alzheimer's Disease
Current Alzheimer Research Vitamin D in COPD - A Pleiotropic Micronutrient in a Multisystem Disease
Current Respiratory Medicine Reviews Essential Hypertension, Cerebral White Matter Pathology and Ischemic Stroke
Current Medicinal Chemistry Effects of Glucagon-like Peptide-1 Receptor Agonists and Sodium-glucose Cotransporter 2 Inhibitors on Cardiorenal and Metabolic Outcomes in People Without Diabetes
Current Pharmaceutical Design Meet Our Editorial Board Member
Current Cardiology Reviews Ansamycin Inhibitors of Hsp90: Natures Prototype for Anti-Chaperone Therapy
Current Topics in Medicinal Chemistry Neglected Tropical Protozoan Diseases: Drug Repositioning as a Rational Option
Current Topics in Medicinal Chemistry