Abstract
The current global portfolio of oncology drugs is unlikely to produce durable disease remission for millions of cancer patients worldwide. This is due, in part, to the existence of so-called cancer stem cells (CSCs), a particularly aggressive type of malignant cell that is capable of indefinite self-replication, is refractory to conventional treatments, and is skilled at spreading and colonizing distant organs. To date, no drugs from big-league Pharma companies are capable of killing CSCs. Why? Quite simply, a classic drug development approach based on mutated genes and pathological protein products cannot efficiently target the plastic, epigenetic proclivity of cancer tissues to generate CSCs. Recent studies have proposed that certain elite metabolites (oncometabolites) and other common metabolites can significantly influence the establishment and maintenance of epigenetic signatures of stemness and cancer. Consequently, cellular metabolism and the core epigenetic codes, DNA methylation and histone modification, can be better viewed as an integrated metaboloepigenetic dimension of CSCs, which we have recently termed cancer metabostemness. By targeting weaknesses in the bridge connecting metabolism and epigenetics, a new generation of metabostemnessspecific drugs can be generated for potent and long-lasting elimination of life-threatening CSCs. Here I evaluate the market potential of re-modeling the oncology drug pipeline by discovering and developing new metabolic approaches able to target the apparently undruggable epigenetic programs that dynamically regulate the plasticity of non-CSC and CSC cellular states.
Keywords: Cancer stem cells, drugs, epigenetics, metabolism, metabostemness.
Current Pharmaceutical Design
Title:The Metaboloepigenetic Dimension of Cancer Stem Cells: Evaluating the Market Potential for New Metabostemness-Targeting Oncology Drugs
Volume: 21 Issue: 25
Author(s): Javier A. Menendez
Affiliation:
Keywords: Cancer stem cells, drugs, epigenetics, metabolism, metabostemness.
Abstract: The current global portfolio of oncology drugs is unlikely to produce durable disease remission for millions of cancer patients worldwide. This is due, in part, to the existence of so-called cancer stem cells (CSCs), a particularly aggressive type of malignant cell that is capable of indefinite self-replication, is refractory to conventional treatments, and is skilled at spreading and colonizing distant organs. To date, no drugs from big-league Pharma companies are capable of killing CSCs. Why? Quite simply, a classic drug development approach based on mutated genes and pathological protein products cannot efficiently target the plastic, epigenetic proclivity of cancer tissues to generate CSCs. Recent studies have proposed that certain elite metabolites (oncometabolites) and other common metabolites can significantly influence the establishment and maintenance of epigenetic signatures of stemness and cancer. Consequently, cellular metabolism and the core epigenetic codes, DNA methylation and histone modification, can be better viewed as an integrated metaboloepigenetic dimension of CSCs, which we have recently termed cancer metabostemness. By targeting weaknesses in the bridge connecting metabolism and epigenetics, a new generation of metabostemnessspecific drugs can be generated for potent and long-lasting elimination of life-threatening CSCs. Here I evaluate the market potential of re-modeling the oncology drug pipeline by discovering and developing new metabolic approaches able to target the apparently undruggable epigenetic programs that dynamically regulate the plasticity of non-CSC and CSC cellular states.
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Cite this article as:
Menendez A. Javier, The Metaboloepigenetic Dimension of Cancer Stem Cells: Evaluating the Market Potential for New Metabostemness-Targeting Oncology Drugs, Current Pharmaceutical Design 2015; 21 (25) . https://dx.doi.org/10.2174/1381612821666150710150327
DOI https://dx.doi.org/10.2174/1381612821666150710150327 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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