Epigenetics in Precision Medicine (Volume 30) (Translational Epigenetics, Volume 30)

In recent years, knowledge of epigenetic mechanisms underlying disease onset and progression has proven crucial for the development of novel early diagnosis and prognosis biomarkers for patient stratification and precision medicine. Epigenetics in Precision Medicine, a new volume in the Translational Epigenetics series, provides a thorough discussion and overview of current developments in clinical epigenetics with special emphasis on epigenetic biomarkers that can be used for clinical diagnosis, prognosis, patient stratification, and treatment monitoring. Disease types discussed include cancer, metabolic disorders, neurodegenerative diseases, bone disease, and immune-related disorders. The book examines the challenges of advancing epigenetics research and translating findings to the clinic and drug discovery in each of these areas, as well as current solutions; chapter authors discuss how to leverage epigenomic technologies, applications, and tools, such as next-generation sequencing, to discover new epigenetic biomarkers in disease and drug studies. Epigenetics in Precision Medicine focuses on complex epigenetic mechanisms in several pathologies, and explores how epigenetics can power the advance of precision medicine, not only by improving in vitro diagnostic and prognostic tools, but by providing new therapeutic approaches to treat human disease. Provides a thorough grounding in epigenetics-driven precision medicine, with emphasis on developing and implementing early diagnosis and prognosis biomarkers, and supporting patient stratification Empowers researchers and clinicians to incorporate epigenetics in new disease research, drug discovery, and clinical practice Features chapter contributions from international leaders in the field Front Cover Translational Epigenetics Series Copyright Contents Contributors Preface Chapter 1: Perspectives and future directions of translational epigenetics in personalized and precision medicine Introduction Diagnostic, prognostic, and therapeutic applications of epigenetics in precision medicine Epigenetic-based therapies Conclusions and perspective References Chapter 2: Translational epigenetics in precision medicine of colorectal cancer Introduction Potential epigenetic biomarkers for CRC Epigenetic biomarkers for CRC based on DNA methylation Epigenetic biomarkers for CRC based on histone posttranslational modifications Epigenetic biomarkers for CRC based on microRNAs In vitro diagnostic tests based on epigenetic biomarkers Epigenetic-based IVD test for CRC The Cologuard stool DNA-based test The Epi proColon 2.0 test The EarlyTect colorectal cancer assay miRPredX-31-3p Colvera colorectal cancer screening triage test The Nu.Q colorectal cancer screening triage test Conclusions and future prospects Conflict of interest Acknowledgments References Chapter 3: Epigenetics in precision medicine of breast cancer Introduction Epigenetics in breast carcinogenesis DNA methylation Histone posttranslational modifications Noncoding RNA-mediated gene regulation DNA methylation as a biomarker for breast cancer Histone posttranslational modifications as a biomarker for breast cancer ncRNAs as a biomarker for breast cancer Dietary epigenetic modulators in precision medicine of breast cancer Conclusions Glossary References Chapter 4: Epigenetics and precision medicine in prostate cancer Introduction Prostate cancer management and therapies Androgen deprivation therapy Treatment of locally advanced or metastatic disease ADT plus docetaxel (chemohormonal therapy) ADT plus abiraterone acetate ADT plus second-generation AR blockers Treatment of castration-resistant prostate cancer Chemotherapy Abiraterone acetate and AR blockers Radium-233 Targeted therapies Immunotherapy Epigenetic gene regulation DNA methylation Histone modifications Cooperation of histone marks Prostate cancer epigenetics DNA methylation in prostate cancer Promoter hypermethylation Global hypomethylation Chromatin remodeling in prostate cancer Histone acetylation Histone methylation and EZH2 Epigenetic dysregulation of AR signaling Modifications of the AR Role of pioneer factors Epigenetic therapies in prostate cancer Conventional epigenetic therapies DNA methyltransferase inhibitors Histone deacetylase and histone acetyltransferase inhibitors Epigenetic agents in combination with conventional therapy Emerging epigenetic targeted therapies Histone methyltransferase and histone demethylase inhibitors Bromodomain and extra-terminal motif inhibitors Novel combination strategies Epigenetic biomarkers of treatment response Response to mainstream therapy Surgery and radiation therapy Chemotherapy Response to targeted therapies PARP inhibitors Epigenetic drugs Conclusion Acknowledgments References Chapter 5: Epigenetics and precision medicine in lung cancer Introduction Epigenetics of lung cancer DNA methylation in lung cancer Histone posttranslational modifications in lung cancer Noncoding RNAs in lung cancer MicroRNAs (miRNAs) Long noncoding RNAs (lncRNA) Diagnostic, prognostic, and therapeutic applications of epigenetics in lung cancer DNA methylation as biomarker for lung cancer Histone posttranslational modifications as biomarkers for lung cancer Noncoding RNAs as biomarkers for lung cancer microRNAs LncRNAs Drug response and therapeutics DNA methylation as therapeutic target in lung cancer Histone posttranslational modifications as therapeutic target in lung cancer Noncoding RNAs as therapeutic targets in lung cancer miRNA LncRNAs Conclusions and perspective References Chapter 6: Epigenetics and precision medicine in bone and soft tissue sarcomas Introduction Osteosarcoma Epigenetic biomarkers in diagnosis and prognosis of osteosarcoma DNA methylation signatures Histone methylation-demethylation Histone acetylation-deacetylation Epigenetic therapeutics in osteosarcoma DNMT inhibitors HDAC inhibitors Combination therapies Epigenetics in CSC phenotype and osteoblastic differentiation Ewing sarcoma Epigenetic diagnostic methods in Ewing sarcoma Methylation patterns in Ewing sarcoma Epigenetic prognostic markers in Ewing sarcoma RASSF2 methylation Epigenetic targets in the treatment of Ewing sarcoma HDAC inhibition therapy Targeting BET proteins in the treatment of Ewing sarcoma Undifferentiated pleomorphic sarcoma Epigenetic diagnostic methods in undifferentiated pleomorphic sarcoma Epigenetic prognostic methods in undifferentiated pleomorphic sarcoma Epigenetic targets in the treatment of undifferentiated pleomorphic sarcoma Synovial sarcoma Epigenetics as a diagnostic tool in synovial sarcoma Methylation patterns in synovial sarcoma Epigenetics as a prognostic tool in synovial sarcoma Prognostic value of EZH2 Epigenetics as a therapeutic tool in synovial sarcoma Therapeutic role of EZH2 HDAC inhibitors in synovial sarcoma Targeting KDM2B Rhabdomyosarcoma Epigenetics for diagnostic testing in rhabdomyosarcoma Epigenetics for prognostic testing in rhabdomyosarcoma Epigenetics as a therapeutic target for rhabdomyosarcoma Histone deacetylases Histone acetyltransferases and readers Lysine methyltransferase and de-methylases DNA methyltransferases Leiomyosarcoma Epigenetics for diagnostic testing in leiomyosarcoma Epigenetics for prognostic testing in leiomyosarcoma Epigenetics as a therapeutic target for leiomyosarcoma Liposarcoma Epigenetics for diagnostic testing in liposarcoma Epigenetics for prognostic testing in liposarcoma Epigenetics as a therapeutic target for liposarcoma Malignant peripheral nerve sheath tumor Epigenetics as a prognostic tool in malignant peripheral nerve sheath tumor Epigenetics as a diagnostic tool in malignant peripheral nerve sheath tumor Epigenetics as a therapeutic tool in malignant peripheral nerve sheath tumor DNMT inhibitors in malignant peripheral nerve sheath tumors HDAC8 inhibitors in malignant peripheral nerve sheath tumors Bromodomain inhibitors in MPNST Fibrosarcoma Epigenetics for diagnostic testing in fibrosarcoma Epigenetics for prognostic testing in fibrosarcoma Epigenetics as a therapeutic target for fibrosarcoma Conclusions References Chapter 7: Epigenetics and precision medicine in skin diseases Introduction Inflammatory skin diseases Psoriasis DNA methylation Histone modifications MicroRNAs Future directions in psoriasis Atopic dermatitis DNA methylation Histone modification MicroRNAs Future directions in atopic dermatitis Connective tissue diseases Systemic lupus erythematosus DNA methylation Histone modifications MicroRNAs Future directions in SLE Systemic sclerosis DNA methylation Histone modifications MicroRNAs Future directions in systemic sclerosis Skin neoplasms Cutaneous T-cell lymphoma Histone modifications DNA methylation MicroRNAs Future directions in CTCL Melanoma DNA methylation Histone modifications MicroRNAs Future directions in melanoma Cutaneous squamous cell carcinoma Conclusions References Chapter 8: Epigenetic biomarker and drug development in gynecological cancers Cervical cancer Papanicolaou smear and HPV testing DNA methylation as a biomarker DNA methylation in cervical cancer Quantitative methylation analysis as a potential biomarker for clinical application PAX1, SOX1, ZNF582, and POU4F3 CADM1, MAL, and miR124-2 EPB41L3 HPV methylation Future perspectives Cytology-based screening: Pap smear+HPV testing+methylation testing Cytology-based screening: Pap smear+methylation testing HPV-based screening: HPV testing+methylation testing Endometrial cancer Molecular characteristics of EC: Genetics and epigenetics DNA methylation as a biomarker Future perspectives Ovarian cancer DNA methylation as a biomarker Limitations of the current ovarian cancer detection methods Molecular detection of ovarian cancer DNA from liquid biopsies (cell-free DNA) DNA from cervical scrapings DNA methylation can be a prognostic marker Epigenetic drug development Epigenetic alterations and their potential role in clinical application in the setting of ovarian cancer Clinical trials of epigenetic modifiers in ovarian cancer Future perspectives Conclusion References Chapter 9: Epigenetics in precision medicine of pancreatic cancer Introduction Epigenetics of pancreatic cancer DNA methylation Histone modifications Histone methylation Histone acetylation Histone ubiquitination Noncoding RNAs microRNAs Long noncoding RNAs Diagnostic, prognostic, and therapeutic applications of epigenetics in pancreatic cancer Epigenetics in PDAC diagnosis Epigenetics in PDAC prognosis Epigenetics in PDAC therapy Conclusions and perspective References Chapter 10: Epigenetics and personalized medicine of brain cancer Introduction A short introduction to CNS tumor biology On tumor ``stemness ́ ́ On brain tumor ``stemness ́ ́ Approaches to the understanding of tumor biology To personalize (therapy) or not to personalize Epigenomics: An introduction Genomic imprinting Epigenetics and cancer Comprehending epigenetics DNA methylation P15/P16 methylation Histone post-translational modifications The special case of G-quadruplexes Therapeutic interventions Enzymes and therapy Acetylation and therapeutic approaches Epigenetic-based therapeutic interventions miRNAs Targeted and personalized therapies Conclusions Declarations Glossary References Chapter 11: Epigenetics and precision medicine in diabetes and obesity prevention and management Introduction Routine diagnostic biomarkers for obesity and T2D Epigenetic regulation and disease Epigenetic mechanisms DNA methylation Post-translational histone modifications (PTMs) Noncoding RNAs (ncRNAs) Precision medicine and epigenetic marks in metabolic disorders Clinical relevance of epigenetic biomarkers in obesity and T2D Epigenetic biomarkers in noninvasive samples Future remarks and conclusion References Chapter 12: Epigenetics in precision medicine of cardiovascular disease Cardiovascular disease Biomarkers Epigenetic biomarkers: Noncoding RNAs Most relevant noncoding RNA subclasses in the field of biomarkers MicroRNAs Long noncoding RNAs Circular RNAs Noncoding RNAs as diagnostic biomarkers of cardiovascular disease Noncoding RNAs as prognostic biomarkers of cardiovascular disease Noncoding RNAs in biomarker-guided therapy of cardiovascular disease Defining clinical phenotypes: Noncoding RNAs and decision tree learning Conclusions Funding Conflict of interests References Chapter 13: Sperm epigenetics: The future of precision medicine in male infertility Disclosures Introduction Epigenetics: Background and history Histone posttranslational modifications DNA methylation Noncoding RNA Epigenetics and fertility Using epigenetic data in predictive modeling to identify and treat male fertility Conclusions and future perspective References Chapter 14: Epigenetic in precision medicine in autoimmune and inflammatory-mediated disorders Introduction Epigenetic bases of autoimmune inflammatory-related diseases Rheumatoid arthritis DNA methylation Histone modifications MiRNAs Inflammatory bowel disease DNA methylation Histone modifications MiRNAs Sjögren syndrome DNA methylation Histone modifications MiRNAs Rheumatoid arthritis Inflammatory bowel disease Sjögren syndrome Conclusions and perspective References Chapter 15: Epigenetics and precision medicine in allergic diseases Introduction Epigenetic modifications Importance of epigenetic changes in allergic diseases Challenges of the tissue-specificity of epigenetic changes Which epigenetic modification might be best suited for translation to clinical settings? Precision medicine in allergic diseases Diagnosis of allergic diseases Predicting the onset, remission, and/or severity of allergic diseases Using epigenetics to define subgroups of allergic patients Epigenetics for personalized treatment decisions using conventional treatment and biologics Corticosteroids Biologics Monitoring the efficiency and success of allergen immunotherapy The epigenome as a target for personalized treatment Altering the epigenetic phenotype though modulation of the microbiome Epigenetic therapy Epigenetic editing Targeting miRNAs in patients with allergic diseases Conclusions References Chapter 16: Epigenetics in spine curvature disorders Introduction Epigenetics in bone metabolism associated to spine deformity DNA methylation Noncoding RNAs Role of miRNAs in AIS Role of miRNAs in DS Epigenetic biomarkers in scoliosis precision medicine DNA methylation biomarkers in AIS precision medicine miRNAs biomarkers in AIS precision medicine Conclusions and future prospects Acknowledgments and funding References Chapter 17: Methylated circulating tumor DNA biomarkers for the blood-based detection of cancer signals Introduction The public health burden of cancer and the need for minimally invasive tests for cancer detection Circulating tumor DNA as a biomarker for the detection of cancer signals Choice of somatic sequence mutation or DNA methylation as ctDNA biomarkers Characteristics and composition of cfDNA and ctDNA ctDNA detection technologies Best preanalytical practices for obtaining high-quality cfDNA templates Blood collection and preanalytical variables Cell-free DNA isolation and quality control Sodium bisulfite conversion of cfDNA for DNA methylation analyses Cell-free DNA assay types Real-time PCR-based assays for targeted loci Next-generation sequencing (NGS)-based assays ``Real-world ́ ́ applications of cfDNA technology to the detection of cancer signals Early detection of cancer via population-based screening Population-based screening for the detection of colorectal cancer using the methylated SEPTIN9, ``mSEPT9 ́ ́ blood-based ctDN ... Development of multicancer screening test based on methylated ctDNA profiles The Galleri test by GRAIL Inc Application of ctDNA technology in oncology for the clinical management of cancer patients Utility of ctDNA testing for monitoring tumor burden in cancer patients Benefits of the detection of molecular residual disease, recurrence, and tumor burden in the setting of colorectal cancer Personalized NGS-based assay for the detection of minimal residual disease and cancer recurrence Methylated ctDNA test for the detection of minimal residual disease and recurrence of CRC Liquid biopsy Liquid biopsy for the prediction of response to treatment Conclusions and future directions References Chapter 18: Dietary regulation of miRNA in precision medicine of lung cancer Introduction Biogenesis of miRNA Role of miRNA in lung cancer progression Cell proliferation and apoptosis Modulation of stemness properties Altering the expression of tumor suppressor genes or oncogenes Altering the metabolic pathways Regulating the expression of immunity-associated genes Role of miRNA in lung cancer chemoresistance Role of miRNAs in lung cancer therapeutics miRNAs as diagnostic tools miRNAs as prognostic tools miRNAs as predictive tools Dietary regulation of miRNA in lung cancer Curcumin Tea catechins Genistein Quercetin Resveratrol Sulforaphane Conclusion and future perspective References Glossary Chapter 19: Epigenetic biomarkers in male infertility and its potential use in assisted reproductive technology Introduction Epigenetics in spermatogenesis and male infertility DNA methylation and male infertility Histones and histone variants and their role in male infertility Histone variants Histone PTMs Histone PTMs as DNA damage sensors in spermatozoa microRNAs and sperm quality The potential of epigenetics to improve clinical management of male infertility Conclusions and future prospects References Index Back Cover