Profound changes in the epigenetic landscape of cancer cells underlie the development of human malignancies. These changes include large-scale DNA methylation changes throughout the genome as well as alterations in the compendium of post-translational chromatin modifications. Epigenetic aberrations impact multiple steps during tumorigenesis, ultimately promoting the selection of neoplastic cells with increasing pathogenicity. Identification of these alterations for use as predictive and prognostic biomarkers has been a highly sought after goal. Recent advances in the field have not only greatly expanded our knowledge of the epigenetic changes driving neoplasia but also demonstrated their significant clinical utility as cancer biomarkers. These biomarkers have proved to be useful for identifying patients whose malignancies are sensitive to specific cytotoxic chemotherapies and may hold promise for predicting which patients will benefit from newer targeted agents directed at oncogenes. The recent application of global analysis strategies has further accelerated our understanding of the epigenome and promises to enhance the identification of epigenomic programs underlying cancer progression and treatment response.
"Cancer phenotypes have a complex and heterogeneous character, which cannot be explained by genetic defects alone . Several groups have shown the crucial role of epigenetic modifications in the manifestation of various cancer types    . Epigenetic modifications are defined as heritable changes in the expression and regulation of gene expression without altering the DNA sequencing . "
[Show abstract][Hide abstract] ABSTRACT: Prostate cancer (PCA) is a major health concern in current times. Ever since prostate specific antigen (PSA) was introduced in clinical practice almost three decades ago, the diagnosis and management of PCA have been revolutionized. With time, concerns arose as to the inherent shortcomings of this biomarker and alternatives were actively sought. Over the past decade new PCA biomarkers have been identified in tissue, blood, urine, and other body fluids that offer improved specificity and supplement our knowledge of disease progression. This review focuses on superiority of circulating biomarkers over tissue biomarkers due to the advantages of being more readily accessible, minimally invasive (blood) or noninvasive (urine), accessible for sampling on regular intervals, and easily utilized for follow-up after surgery or other treatment modalities. Some of the circulating biomarkers like PCA3, IL-6, and TMPRSS2-ERG are now detectable by commercially available kits while others like microRNAs (miR-21, -221, -141) and exosomes hold potential to become available as multiplexed assays. In this paper, we will review some of these potential candidate circulating biomarkers that either individually or in combination, once validated with large-scale trials, may eventually get utilized clinically for improved diagnosis, risk stratification, and treatment.
[Show abstract][Hide abstract] ABSTRACT: For many years cancer research has focused on genetic defects, but during the last decade epigenetic deregulation has been increasingly recognized as a hallmark of cancer. The advent of genome-scale analysis techniques, including the recently developed next-generation sequencing, has enabled an invaluable advance in the molecular mechanisms underlying tumor initiation, progression, and expansion. In this review we describe recent advances in the field of cancer epigenomics concerning DNA methylation, histone modifications, and miRNAs. In the near future, this information will be used to generate novel biomarkers of relevance to diagnosis, prognosis, and chemotherapeutic response.
Current opinion in genetics & development 03/2012; 22(1):50-5. DOI:10.1016/j.gde.2012.02.008 · 7.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Epigenetic therapy reverting aberrant acetylation or methylation offers the possibility to target preferentially tumor cells and to preserve normal cells. Combination epigenetic therapy may further improve the effect of individual drugs. We investigated combined action of demethylating agent decitabine and histone deacetylase inhibitor SAHA (Vorinostat) on different leukemic cell lines in comparison with peripheral blood lymphocytes. Large decrease of viability, as well as huge p21WAF1 induction, reactive oxygen species formation, and apoptotic features due to combined decitabine and SAHA action were detected in leukemic cell lines irrespective of their p53 status, while essentially no effect was observed in response to the combined drug action in normal peripheral blood lymphocytes of healthy donors. p53-dependent apoptotic pathway was demonstrated to participate in the wtp53 CML-T1 leukemic cell line response, while significant influence of reactive oxygen species on viability decrease has been detected in p53-null HL-60 cell line.
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