Article ; Online: Metabolic targeting of malignant tumors: small-molecule inhibitors of bioenergetic flux.
Recent patents on anti-cancer drug discovery
2010 Volume 6, Issue 1, Page(s) 6–14
Abstract: Metabolism in tumors deviates significantly from that of normal tissues. Increasingly, the underlying aberrant metabolic pathways are being considered as novel targets for cancer therapy. Denoted "metabolic targeting", small molecule drugs are under ... ...
Abstract | Metabolism in tumors deviates significantly from that of normal tissues. Increasingly, the underlying aberrant metabolic pathways are being considered as novel targets for cancer therapy. Denoted "metabolic targeting", small molecule drugs are under investigation for focused inhibition of key metabolic steps that are utilized by tumors, since such inhibitors should harbor minimal toxicity towards surrounding normal tissues. This review will examine the primary biochemical pathways that tumors harness to enhance their bioenergetic capacity, which in turn, help their rapid proliferation and metastasis within the host. It is hoped that "metabolite-mimetic" drugs can be utilized to interfere with metabolic flux pathways active within the tumor, and across tumor-microenvironment boundary. In fact, the major pathways of mammalian metabolism, i.e., the carbohydrate, amino-acid, and fatty-acid metabolic pathways have been examined as putative targets for drug development, with some drug candidates advancing to phase II/III stages. In this regard, glucose metabolism, i.e., the glycolytic pathway - that predominates the bio-energetic flux in tumors, and the associated mitochondrial metabolism have received the most attention as suitable "druggable" targets, focused either at the pathway enzymes or at the plasma-membrane-bound metabolite transporters. Outlined in this review are pre-clinical studies that have led to the discovery of promising drug candidates to target tumor-metabolic flux, and ensuing patents, with descriptions of the biochemical rationale for the combinatorial strategy of a particular metabolic pathway-drug candidate pair. |
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MeSH term(s) | Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Energy Metabolism/drug effects ; Energy Metabolism/genetics ; Enzyme Inhibitors/therapeutic use ; Glycolysis/drug effects ; Glycolysis/genetics ; Humans ; Metabolic Networks and Pathways/drug effects ; Metabolic Networks and Pathways/genetics ; Models, Biological ; Molecular Targeted Therapy/methods ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/metabolism ; Small Molecule Libraries |
Chemical Substances | Antineoplastic Agents ; Enzyme Inhibitors ; Small Molecule Libraries |
Language | English |
Publishing date | 2010-11-29 |
Publishing country | United Arab Emirates |
Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review |
ZDB-ID | 2250820-X |
ISSN | 2212-3970 ; 1574-8928 |
ISSN (online) | 2212-3970 |
ISSN | 1574-8928 |
DOI | 10.2174/157489211793980114 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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