- Email: [email protected]
Cancer epigenetics as biomarkers of clinical significance
Cancer Letters 342 (2014) 168–169
Contents lists available at ScienceDirect
Cancer Letters journal homepage: www.elsevier.com/locate/canlet
Editorial
Cancer epigenetics as biomarkers of clinical significance Cancer is a multistage process characterized by a number of alterations in a number of key cellular processes including, among others, limitless potential for replication, sustained angiogenesis, self-sufficiency in growth, evasion of apoptosis, etc. Throughout these processes, a number of genes become deregulated and although, for some of them, their mechanism (by which they are involved in carcinogenesis) is somewhat established, there is still a gap in our understanding as to how they are involved and how their expression is regulated. To this end, over the years, numerous attempts have been made in order to identify cancer-specific alterations capable of regulating gene expression during malignant transformation. With the term ‘epigenetics’ we refer to heritable and reversible changes in gene expression and chromatin organization which are independent of the DNA coding sequence itself. Thus, epigenetic processes (DNA methylation, histone modifications, etc.) can modulate and control gene expression whereas their deregulation can contribute to altered gene expression associated with the multistage carcinogenic process. Given the reversible nature of such epigenetic modifications, a number of chemical entities have been identified on the basis of potentiating therapeutic outcome and also as a means of intervention and/or cancer prevention (when utilized as dietary supplements). Finally, only recently, a large number of studies have identified cancer-specific epigenetic alterations in an attempt to utilize them as cancer biomarkers for prognosis and/or diagnosis. This, in turn, is of utmost importance because of their potential clinical significance and overall patient management. My goal as a Guest Editor of this Special Issue was to provide the current state of cancer epigenetic modifications as potential biomarkers of clinical significance with emphasis on diagnosis, prognosis, prevention and therapeutic outcome in a number of most prevalent human cancers. To this end, Dr. Hoon and colleagues review the role of epigenetic aberrations in cutaneous melanoma tumorigenesis and progression with particular emphasis on their utilization as biomarkers of therapeutics and overall patient management. Special emphasis is given in epigenetic melanoma biomarker development and verification of clinical utility. Dr. Worsham and colleagues review the role of epigenetics in the development of neoplasia, its transformation, progression and recurrence in pre-invasive squamous head and neck carcinoma (HNSCC) lesions. Special emphasis is given on the role of promoter hypermethylation of tumor suppressor genes in the progression from benign papillomas to malignancy in HNSCC. Dr. Kreth and colleagues review the basic principles of epigenetic control in gliomas, their current and putative future role in prognostic and predictive models and possible interactions within the epigenetic network. In addition, special emphasis is given on 0304-3835/$ - see front matter Ó 2013 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.canlet.2013.10.027
the diagnostic and therapeutic opportunities at the forefront of the epigenetic research field as well as the current and future clinical workflow models for the molecular characterization of malignant gliomas. Drs. Kaz and Grady review the status of identified candidate epigenetic biomarkers for Barrett’s esophagus (BE), esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). These include aberrantly methylated genes associated with early detection or diagnostic markers as well as estimating prognosis and/or predicting response to treatment. Finally, special emphasis is given on challenges need to be overcome for developing clinically relevant esophageal cancer biomarkers. Dr. Liloglou and colleagues review the role of potential epigenetic biomarkers (DNA methylation and miRNAs) in assisting the clinical management of lung cancer. To this end, special emphasis is given on the validation steps necessary for the development of epigenetic biomarkers towards clinical implementation and the weaknesses of current biomarker studies. Dr. Georgakilas and colleagues review the prevalence of epigenetic modifications on breast cancer and how epigenetic research has led to improved survival of these patients primarily through the use of drugs that alter DNA methylation and histone acetylation. Moreover, special emphasis is given on other clinical applications of epigenetics including cancer screening and early detection, prevention, classification for epidemiology and prognostic purposes as well as predicting outcomes after standard therapy. Drs. Pogribny and Rusyn review the current knowledge on the role of epigenetic aberrations (DNA methylation, histone modifications and miRNAs) in the pathogenesis of hepatocellular carcinoma (HCC). Special emphasis is given on epigenetic modifications underlying the detection, therapeutic intervention and prevention of hepatocarcinogenesis. Drs. Fukushige and Horii review the role of epigenetic biomarkers in pancreatic cancer progression with special emphasis on DNA methylation, miRNAs, satellite repeats and histone modifications for early diagnosis. Dr. Coppede reviews the role of DNA methylation biomarkers in the multi-step process of colorectal cancer (CRC) and especially those biomarkers associated with diagnsosis, progression, invasion and metastasis, prognosis and response to treatment in CRC. Moreover, special emphasis is given on the complex interactions among dietary one-carbon nutrients (folates, vitamin B6, B12, methionine, etc.), their metabolic genes, CRC risk and associated DNA methylation profiles in CRC. Dr. Bianco-Miotto & colleagues review the role of epigenetic modifications in prostate tumorigenesis with particular emphasis on those involved in the development and progression stages of prostate cancer with the aim to provide novel therapeutic targets as well as prognostic and diagnostic markers.
Editorial / Cancer Letters 342 (2014) 168–169
Drs. Samimi and Gloss review the role of cancer-specific DNA methylation changes in candidate genes with potential clinical utility as biomarkers of diagnosis, prognosis and/or therapeutic outcome in epithelial ovarian cancer. To this end, special emphasis is given on the identification of sensitive and robust panels of markers and the standardization of techniques required in order improving detection and patient outcome. Drs. Jeronimo and Henrique review the current state on the development of epigenetic-based genitourinary (GU) neoplasms (e.g. prostate, bladder, kidney and testis) with the aim to emphasize on those most promising to revolutionize the clinical management of GU cancer patients. Finally, Drs. Herceq and Lee review the epidemiological and laboratory-based evidence of those chemical agents capable of altering the epigenome and thus exert their anti-neoplastic effects against different cancer types. Special emphasis is given on those chemical entities that can modulate the epigenome and thus potentially capable of preventing human cancer development when administered as dietary supplements.
169
I would like to express my gratitude to all authors for contributing their expertise in this special issue of Cancer Letters in ‘‘Cancer Epigenetics as Biomarkers of Clinical Significance’’. Last, but certainly not least, I would like to thank Prof. Manfred Schwab (Editor-in-Chief), for the opportunity he has given me to construct this Special Issue as well as Jo Hodgkison (Editorial Office) for her patience and support throughout the process of putting this Special Issue together. Mihalis I. Panayiotidis School of Life Sciences, Heriot Watt University, John Muir Building, Riccarton Campus, Edinburgh, EH14 4AS, Scotland, UK Tel.: +44 (0)131 451 4313. E-mail address: [email protected]
Contents lists available at ScienceDirect
Cancer Letters journal homepage: www.elsevier.com/locate/canlet
Editorial
Cancer epigenetics as biomarkers of clinical significance Cancer is a multistage process characterized by a number of alterations in a number of key cellular processes including, among others, limitless potential for replication, sustained angiogenesis, self-sufficiency in growth, evasion of apoptosis, etc. Throughout these processes, a number of genes become deregulated and although, for some of them, their mechanism (by which they are involved in carcinogenesis) is somewhat established, there is still a gap in our understanding as to how they are involved and how their expression is regulated. To this end, over the years, numerous attempts have been made in order to identify cancer-specific alterations capable of regulating gene expression during malignant transformation. With the term ‘epigenetics’ we refer to heritable and reversible changes in gene expression and chromatin organization which are independent of the DNA coding sequence itself. Thus, epigenetic processes (DNA methylation, histone modifications, etc.) can modulate and control gene expression whereas their deregulation can contribute to altered gene expression associated with the multistage carcinogenic process. Given the reversible nature of such epigenetic modifications, a number of chemical entities have been identified on the basis of potentiating therapeutic outcome and also as a means of intervention and/or cancer prevention (when utilized as dietary supplements). Finally, only recently, a large number of studies have identified cancer-specific epigenetic alterations in an attempt to utilize them as cancer biomarkers for prognosis and/or diagnosis. This, in turn, is of utmost importance because of their potential clinical significance and overall patient management. My goal as a Guest Editor of this Special Issue was to provide the current state of cancer epigenetic modifications as potential biomarkers of clinical significance with emphasis on diagnosis, prognosis, prevention and therapeutic outcome in a number of most prevalent human cancers. To this end, Dr. Hoon and colleagues review the role of epigenetic aberrations in cutaneous melanoma tumorigenesis and progression with particular emphasis on their utilization as biomarkers of therapeutics and overall patient management. Special emphasis is given in epigenetic melanoma biomarker development and verification of clinical utility. Dr. Worsham and colleagues review the role of epigenetics in the development of neoplasia, its transformation, progression and recurrence in pre-invasive squamous head and neck carcinoma (HNSCC) lesions. Special emphasis is given on the role of promoter hypermethylation of tumor suppressor genes in the progression from benign papillomas to malignancy in HNSCC. Dr. Kreth and colleagues review the basic principles of epigenetic control in gliomas, their current and putative future role in prognostic and predictive models and possible interactions within the epigenetic network. In addition, special emphasis is given on 0304-3835/$ - see front matter Ó 2013 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.canlet.2013.10.027
the diagnostic and therapeutic opportunities at the forefront of the epigenetic research field as well as the current and future clinical workflow models for the molecular characterization of malignant gliomas. Drs. Kaz and Grady review the status of identified candidate epigenetic biomarkers for Barrett’s esophagus (BE), esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). These include aberrantly methylated genes associated with early detection or diagnostic markers as well as estimating prognosis and/or predicting response to treatment. Finally, special emphasis is given on challenges need to be overcome for developing clinically relevant esophageal cancer biomarkers. Dr. Liloglou and colleagues review the role of potential epigenetic biomarkers (DNA methylation and miRNAs) in assisting the clinical management of lung cancer. To this end, special emphasis is given on the validation steps necessary for the development of epigenetic biomarkers towards clinical implementation and the weaknesses of current biomarker studies. Dr. Georgakilas and colleagues review the prevalence of epigenetic modifications on breast cancer and how epigenetic research has led to improved survival of these patients primarily through the use of drugs that alter DNA methylation and histone acetylation. Moreover, special emphasis is given on other clinical applications of epigenetics including cancer screening and early detection, prevention, classification for epidemiology and prognostic purposes as well as predicting outcomes after standard therapy. Drs. Pogribny and Rusyn review the current knowledge on the role of epigenetic aberrations (DNA methylation, histone modifications and miRNAs) in the pathogenesis of hepatocellular carcinoma (HCC). Special emphasis is given on epigenetic modifications underlying the detection, therapeutic intervention and prevention of hepatocarcinogenesis. Drs. Fukushige and Horii review the role of epigenetic biomarkers in pancreatic cancer progression with special emphasis on DNA methylation, miRNAs, satellite repeats and histone modifications for early diagnosis. Dr. Coppede reviews the role of DNA methylation biomarkers in the multi-step process of colorectal cancer (CRC) and especially those biomarkers associated with diagnsosis, progression, invasion and metastasis, prognosis and response to treatment in CRC. Moreover, special emphasis is given on the complex interactions among dietary one-carbon nutrients (folates, vitamin B6, B12, methionine, etc.), their metabolic genes, CRC risk and associated DNA methylation profiles in CRC. Dr. Bianco-Miotto & colleagues review the role of epigenetic modifications in prostate tumorigenesis with particular emphasis on those involved in the development and progression stages of prostate cancer with the aim to provide novel therapeutic targets as well as prognostic and diagnostic markers.
Editorial / Cancer Letters 342 (2014) 168–169
Drs. Samimi and Gloss review the role of cancer-specific DNA methylation changes in candidate genes with potential clinical utility as biomarkers of diagnosis, prognosis and/or therapeutic outcome in epithelial ovarian cancer. To this end, special emphasis is given on the identification of sensitive and robust panels of markers and the standardization of techniques required in order improving detection and patient outcome. Drs. Jeronimo and Henrique review the current state on the development of epigenetic-based genitourinary (GU) neoplasms (e.g. prostate, bladder, kidney and testis) with the aim to emphasize on those most promising to revolutionize the clinical management of GU cancer patients. Finally, Drs. Herceq and Lee review the epidemiological and laboratory-based evidence of those chemical agents capable of altering the epigenome and thus exert their anti-neoplastic effects against different cancer types. Special emphasis is given on those chemical entities that can modulate the epigenome and thus potentially capable of preventing human cancer development when administered as dietary supplements.
169
I would like to express my gratitude to all authors for contributing their expertise in this special issue of Cancer Letters in ‘‘Cancer Epigenetics as Biomarkers of Clinical Significance’’. Last, but certainly not least, I would like to thank Prof. Manfred Schwab (Editor-in-Chief), for the opportunity he has given me to construct this Special Issue as well as Jo Hodgkison (Editorial Office) for her patience and support throughout the process of putting this Special Issue together. Mihalis I. Panayiotidis School of Life Sciences, Heriot Watt University, John Muir Building, Riccarton Campus, Edinburgh, EH14 4AS, Scotland, UK Tel.: +44 (0)131 451 4313. E-mail address: [email protected]