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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Science: general issues --- Neurosciences --- organoids --- editorial --- neurological disorder --- neurodegenenerative diseases --- brain development

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Science: general issues --- Pharmacology --- Epigenome --- Diseases epigenome --- Histone variants --- histone modification --- DNA methylation --- small molecules --- oncology --- non-coding RNA --- Drug transporters --- epigenetic biomarkers --- organoids model

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Science: general issues --- Pharmacology --- Epigenome --- Diseases epigenome --- Histone variants --- histone modification --- DNA methylation --- small molecules --- oncology --- non-coding RNA --- Drug transporters --- epigenetic biomarkers --- organoids model --- Epigenome --- Diseases epigenome --- Histone variants --- histone modification --- DNA methylation --- small molecules --- oncology --- non-coding RNA --- Drug transporters --- epigenetic biomarkers --- organoids model

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Summary of Genes. Thirty years ago, the gene responsible for cystic fibrosis (CF), a recessive genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene, was identified. This progress has considerably changed our understanding of the pathophysiology of CF and has paved the way for the development of novel and specific therapies for the disease. The CFTR gene contains 27 exons and is characterized by a frequent three base pair deletion of the p.Phe508del. As a result of collaborative work, today more than 2000 mutations have been reported in the gene, and their impact on protein function is now more evident and useful in designing new strategies to correct the gene defect. The field of gene therapy, as illustrated by Ziying Yan in this book, has worked on identifying an efficient vector system for the delivery of the wild-type CFTR gene to the lung. At the same time, animal models have been developed in mice, rats, rabbits, zebrafish, ferrets, and pigs to establish the efficacity of gene delivery. These animals are also of the utmost importance in testing new molecules as modulators or correctors to improve the CFTR lung function. During the last three decades, the epidemiology of CF has dramatically changed, as today cystic fibrosis is now a chronic adult pulmonary disease.

Medicine --- cystic fibrosis --- Staphylococcus aureus --- superantigen --- enterotoxin gene cluster --- MRSA --- exosomes --- microvesicles --- lung --- primary cells --- newborn screening --- trypsinogen --- CFTR gene --- next generation sequencing --- health policy --- rAAV2/HBoV1 --- baculovirus --- insect cells --- lung microbiome --- metagenomics --- gut–lung axis --- Cystic fibrosis --- CFTR --- transcriptomics --- proteostasis --- small molecules --- drug development --- common and new pathogenic variants --- ethnic Russian population --- gene therapy --- cyclophosphamide --- transient immunosuppression --- incidence --- survival --- genotype-phenotype correlations --- health policies --- CFTR modulators --- human nasal epithelial cells --- organoids --- biomarker --- functional assay --- pre-clinical in vitro models --- CFTR-related disorders --- molecular diagnosis --- CFTR variants --- Next Generation Sequencing (NGS) --- disease liability --- interpretation --- penetrance --- genotype-guided therapy --- miRNA --- airway basal cell --- lentivirus --- cystic fibrosis --- Staphylococcus aureus --- superantigen --- enterotoxin gene cluster --- MRSA --- exosomes --- microvesicles --- lung --- primary cells --- newborn screening --- trypsinogen --- CFTR gene --- next generation sequencing --- health policy --- rAAV2/HBoV1 --- baculovirus --- insect cells --- lung microbiome --- metagenomics --- gut–lung axis --- Cystic fibrosis --- CFTR --- transcriptomics --- proteostasis --- small molecules --- drug development --- common and new pathogenic variants --- ethnic Russian population --- gene therapy --- cyclophosphamide --- transient immunosuppression --- incidence --- survival --- genotype-phenotype correlations --- health policies --- CFTR modulators --- human nasal epithelial cells --- organoids --- biomarker --- functional assay --- pre-clinical in vitro models --- CFTR-related disorders --- molecular diagnosis --- CFTR variants --- Next Generation Sequencing (NGS) --- disease liability --- interpretation --- penetrance --- genotype-guided therapy --- miRNA --- airway basal cell --- lentivirus

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Improved understanding of the cellular and molecular makeup of tumors in the last 30 years has unraveled a previously unexpected level of heterogeneity among tumor cells as well as within the tumor microenvironment. The concept of tumor heterogeneity underlines the realization that different tumors can display significant differences in their genomic content as well as in their overall behavior. Our capacity to better understand the heterogeneous make up of tumors has very important consequences on our ability to design efficient therapeutic strategies to improve patient survival. This book highlights several aspects of tumor heterogeneity in the context of metastatic development and summarize some of the challenges posed by heterogeneity for tumor diagnostics and therapeutic management of tumors.

Medicine --- clear cell renal cell carcinoma --- tumor evolution --- tumor ecology --- intratumor heterogeneity --- multisite tumor sampling --- targeted therapy --- uterine carcinosarcoma --- endometrial carcinoma --- metaplastic carcinoma --- epithelial-to-mesenchymal transition --- clonality --- mutation --- TP53 --- PI3K/AKT pathway --- gene expression --- miRNA expression --- tumor microenvironment --- interstitial pH --- acidosis --- tumor heterogeneity --- magnetic resonance imaging --- hyperpolarized 13C MRI --- carbonic anhydrase --- lactic acid --- positron emission tomography --- esophageal squamous cell carcinoma --- precision medicine --- natural killer cells --- tumor mutation burden --- immunotherapy --- PET --- heterogeneity --- radiomics --- radiopharmaceuticals --- SUV --- nuclear medicine --- colon cancer --- Wnt signaling --- phenotypic plasticity --- EMT --- hybrid E/M --- collective and single-cell migration --- beta-catenin paradox --- breast cancer --- immune microenvironment --- DCIS --- ADH --- mammary gland --- cell fate --- 3D cultures --- organoids --- signaling --- single-cell RNAseq --- tumor endothelial cell --- metastasis --- angiocrine factor --- microsatellite instability --- colorectal cancer --- immune checkpoints --- deficient mismatch repair --- plasticity --- biomechanics --- circulating tumor cells (CTCs) --- extracellular vesicles --- metastatic niche --- epigenetics --- CTC-clusters --- single-cell analysis --- cellular heterogeneity --- circulating tumor cells --- pancreatic cancer --- epithelial mesenchymal plasticity --- target discovery --- review --- genomics --- intra-tumour heterogeneity --- subclonal diversity --- treatment resistance --- clear cell renal cell carcinoma --- tumor evolution --- tumor ecology --- intratumor heterogeneity --- multisite tumor sampling --- targeted therapy --- uterine carcinosarcoma --- endometrial carcinoma --- metaplastic carcinoma --- epithelial-to-mesenchymal transition --- clonality --- mutation --- TP53 --- PI3K/AKT pathway --- gene expression --- miRNA expression --- tumor microenvironment --- interstitial pH --- acidosis --- tumor heterogeneity --- magnetic resonance imaging --- hyperpolarized 13C MRI --- carbonic anhydrase --- lactic acid --- positron emission tomography --- esophageal squamous cell carcinoma --- precision medicine --- natural killer cells --- tumor mutation burden --- immunotherapy --- PET --- heterogeneity --- radiomics --- radiopharmaceuticals --- SUV --- nuclear medicine --- colon cancer --- Wnt signaling --- phenotypic plasticity --- EMT --- hybrid E/M --- collective and single-cell migration --- beta-catenin paradox --- breast cancer --- immune microenvironment --- DCIS --- ADH --- mammary gland --- cell fate --- 3D cultures --- organoids --- signaling --- single-cell RNAseq --- tumor endothelial cell --- metastasis --- angiocrine factor --- microsatellite instability --- colorectal cancer --- immune checkpoints --- deficient mismatch repair --- plasticity --- biomechanics --- circulating tumor cells (CTCs) --- extracellular vesicles --- metastatic niche --- epigenetics --- CTC-clusters --- single-cell analysis --- cellular heterogeneity --- circulating tumor cells --- pancreatic cancer --- epithelial mesenchymal plasticity --- target discovery --- review --- genomics --- intra-tumour heterogeneity --- subclonal diversity --- treatment resistance