[Epigenetic perturbations and cancer: innovative therapeutic strategies against cancer].
A complex system of molecular milestones ensures labelling of the genome, driving its organization and functions. These milestones correspond to particular marks associated to active and repressed genes, as well as to non-coding regions or those containing repetitive sequences. Most of these marks are chemical modifications of DNA, corresponding to cytosine methylation, or various posttranslational modifications of histones, the proteins which package the genome. These chemical modifications of DNA or histones are reversible and are catalysed and removed by enzymatic activities associated with factors ensuring critical cellular functions. Indeed, these enzymes are directly connected with signalling pathways, sensing extra- and intracellular environments. Altogether these mechanisms globally control the expression status of genes in each cell, meaning that certain genes are kept active, while most of the genome remains silent. Subtle metabolic changes or intra and extracellular modifications, by altering the marking associated to genes, can have long-term consequences on their expression status. Genes coding for essential regulators of cellular proliferation and differentiation could be among these genes, such as tumor suppressor genes for instance. Hence the knowledge of all these so-called "epigenetic" mechanisms will shed new light on the environmental impact on the control of gene expression and associated diseases, including malignant transformation. The understanding of these mechanisms will also pave the way for innovative therapeutic strategies to fight cancer. This review is aiming to give an overview to the reader of the relevance of epigenetic mechanisms for the understanding and treatment of cancer.
Inserm U823, Université Joseph-Fourier, Institut Albert-Bonniot, 38700 Grenoble, France.
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Rousseaux
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Khochbin
D000074183:ATPases Associated with Diverse Cellular Activities; D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000502:physiology; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000502:physiology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D044127:Epigenesis, Genetic / Q000502:physiology*; D057890:Epigenomics; D015870:Gene Expression; D005819:Genetic Markers / Q000235:genetics; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006657:Histones / Q000235:genetics; D006801:Humans; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D009687:Nuclear Proteins / Q000502:physiology; D015513:Oncogene Proteins / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D000092468:Bromodomain Containing Proteins
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases; D004247:DNA; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005819:Genetic Markers; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C109570:BRDT protein, human; D000092468:Bromodomain Containing Proteins; C000630260:NUTM1 protein, human; C544857:ATAD2 protein, human