Preface

Molecular medicine is an applied science focused on human genes/transcripts, proteins, metabolites, and metabolic networks that describe molecular and cellular processes of health and disease onset and progression. Molecular medicine aims to define associated predictive, diagnostic, and treatment assessment biomarkers for personalized diagnostic/therapeutic strategies, and for a targeted approach to providing the best healthcare for the twenty-first century. Here, in *Molecular Medicine*, a collection of scientific contributions addressing specifically the field of molecular biology and genetics, genetic epidemiology, laboratory medicine, molecular diagnosis, next-generation sequencing, mass spectrometry, omics technologies, biomarker discovery, liquid biopsy, cell heterogeneity, circulating tumor cells, cancer, *inflammation,* infectious diseases, systemic and chronic diseases, neurodegenerative disorders, pharmacogenetics and pharmacogenomics, and precision/personalized medicine is presented.

In the first chapter entitled "Introductory Chapter: Insight into the OMICS Technologies and Molecular Medicine" by Sinem Nalbantoglu and Abdullah Karadag, an overview of the latest headlines of molecular medicine, including promising research strategies and their emerging roles in biomedical research, has been compiled. Throughout the chapter, primary objectives of molecular medicine, involving prediction of potential future pathologies, identifying disease state through effective screening and early diagnosis systems, decision-making on effective treatment strategies, monitoring prognosis and health status, as well as predicting recurrence earlier to apply alternative treatments, have been emphasized.

In the chapter "Precision Medicine—Role of Biomarkers in Early Prediction and Diagnosis of Alzheimer's Disease" by Liming Shen, Sijian Xia, Huajie Zhang, Fang Yao, Xukun Liu, Yuxi Zhao, Ming Ying, Javed Iqbal, and Qiong Liu, the authors precisely outline clinical biomarkers and precision medicine for Alzheimer's disease, which is a chronic and irreversible neurodegenerative disorder. In this chapter, the authors introduce promising research efforts and progress in the development and validation of invasive, minimally invasive, and non-invasive personalized diagnostic strategies and their applications, neuroimaging techniques and neurochemical assays, novel ultrasensitive immunoassay, genetic testing, mass spectrometry methods, metabolomics, and exosomes.

Munindra Ruwali, the author of the chapter "Pharmacogenetics and Cancer Treatment: Progress and Prospects," contributes a comprehensive review on the developments and recent advances in cancer research, pharmacogenetics, and oncogenetics. As precisely addressed by the author throughout the chapter, cancer pharmacogenetics has great importance for considering genotypic and phenotypic heterogeneity among patients, and offering personalized treatment leads to improved response to therapy and decreased side effects in individuals.

Laure Cayrefourcq and Catherine Alix-Panabières, in their chapter "CTCs as Liquid Biopsy: Where Are We Now?," comprehensively examine and summarize the latest findings on detection and characterization strategies of circulating tumor cells (CTCs) in different tumor types together with their advantages and challenges. The authors also discuss other potential circulating biomarkers to be used as liquid biopsy in oncology, and conclude that liquid biopsy diagnostics might be a promising oncotheranostics strategy.

In the chapter by Na Li, Xiaohan Zhan, and Xianquan Zhan, entitled "Energy Metabolism Heterogeneity-based Molecular Biomarkers for Ovarian Cancer,'' the authors search for promising clinical biomarkers for ovarian cancers considering the fact that energy metabolism heterogeneity, namely the Warburg and reverse Warburg effect, coexist in cancers. As thoroughly explained by the authors, the uniqueness of their approach is to look beyond blocking both the Warburg effect and the reverse Warburg effect. Indeed, by implementing an integrative analysis of transcriptomics, proteomics, and mitochondrial proteomics, the authors provide new molecular insights into the promising energy metabolism-based target treatments for ovarian cancer patients.

In the chapter "A novel P53/POMC/Gas/SASH1 Autoregulatory Feedback Loop Activates Mutated SASH1 to Cause Pathologic Hyperpigmentation" by Ding'an Zhou, Jiawei Zeng, Pingshen Hu, and Xiaodong Su, the authors focus on the interaction of p53 with other transduction pathways in a cell model. Their approach is directed to enrich and redefine the p53-responsive genes and their associations. The findings led to the conclusion that understanding the interactions of the p53-responsive genes will elucidate the p53-programmed responses to stress and pathological conditions.

The chapter entitled "Molecular Diagnosis of Invasive Aspergillosis (IA)" by María del Rocío Reyes-Montes, Esperanza Duarte-Escalante María Guadalupe Frías-De-León, Erick Obed Martínez-Herrera, and Gustavo Acosta-Altamirano refers to the epidemiology and molecular diagnosis methods for the detection of the disease and associated challenges. As explained by the authors, molecular diagnosis is superior to the conventional tests in terms of detection reliability, sensitivity, and specificity.

The chapter entitled "Metabolomics: Basic Principles and Applications" by Sinem Nalbantoglu examines the latest and most promising of the emerging highthroughput omics technologies, as one of the system's medicine components, metabolomics. The chapter offers a brief overview of the field focusing on methodological advances, strategies, and challenges, as well as current and future bioapplications.

Principally, *Molecular Medicine* provides a glimpse into the latest developments of systems and molecular medicine, highlighting the emerging high-throughput technologies, promising potential applications, and progress in the development

**V**

of technological and biomedical strategies. The book offers supportive updated

**Dr. Sinem Nalbantoglu, PhD** Molecular Oncology Laboratory,

Kocaeli, Turkey

**Dr. Hakima Amri, PhD**

Washington, DC, USA

TUBITAK Marmara Research Center,

Division of Integrative Physiology, Georgetown University Medical Center,

Gene Engineering and Biotechnology Institute,

Professor of Physiology, Biochemistry, Graduate Education, Department of Biochemistry and Cellular and Molecular Biology,

content for both medical students and healthcare providers.

of technological and biomedical strategies. The book offers supportive updated content for both medical students and healthcare providers.

### **Dr. Sinem Nalbantoglu, PhD**

Molecular Oncology Laboratory, Gene Engineering and Biotechnology Institute, TUBITAK Marmara Research Center, Kocaeli, Turkey

### **Dr. Hakima Amri, PhD**

Professor of Physiology, Biochemistry, Graduate Education, Department of Biochemistry and Cellular and Molecular Biology, Division of Integrative Physiology, Georgetown University Medical Center, Washington, DC, USA

**IV**

Laure Cayrefourcq and Catherine Alix-Panabières, in their chapter "CTCs as Liquid Biopsy: Where Are We Now?," comprehensively examine and summarize the latest findings on detection and characterization strategies of circulating tumor cells (CTCs) in different tumor types together with their advantages and challenges. The authors also discuss other potential circulating biomarkers to be used as liquid biopsy in oncology, and conclude that liquid biopsy diagnostics might be a

In the chapter by Na Li, Xiaohan Zhan, and Xianquan Zhan, entitled "Energy Metabolism Heterogeneity-based Molecular Biomarkers for Ovarian Cancer,'' the authors search for promising clinical biomarkers for ovarian cancers considering the fact that energy metabolism heterogeneity, namely the Warburg and reverse Warburg effect, coexist in cancers. As thoroughly explained by the authors, the uniqueness of their approach is to look beyond blocking both the Warburg effect and the reverse Warburg effect. Indeed, by implementing an integrative analysis of transcriptomics, proteomics, and mitochondrial proteomics, the authors

provide new molecular insights into the promising energy metabolism-based target

interaction of p53 with other transduction pathways in a cell model. Their approach is directed to enrich and redefine the p53-responsive genes and their associations. The findings led to the conclusion that understanding the interactions of the p53-responsive genes will elucidate the p53-programmed responses to stress and

The chapter entitled "Molecular Diagnosis of Invasive Aspergillosis (IA)" by María del Rocío Reyes-Montes, Esperanza Duarte-Escalante María Guadalupe Frías-De-León, Erick Obed Martínez-Herrera, and Gustavo Acosta-Altamirano refers to the epidemiology and molecular diagnosis methods for the detection of the disease and associated challenges. As explained by the authors, molecular diagnosis is superior to the conventional tests in terms of detection reliability, sensitivity, and

The chapter entitled "Metabolomics: Basic Principles and Applications" by Sinem Nalbantoglu examines the latest and most promising of the emerging highthroughput omics technologies, as one of the system's medicine components, metabolomics. The chapter offers a brief overview of the field focusing on

methodological advances, strategies, and challenges, as well as current and future

Principally, *Molecular Medicine* provides a glimpse into the latest developments of systems and molecular medicine, highlighting the emerging high-throughput technologies, promising potential applications, and progress in the development

In the chapter "A novel P53/POMC/Gas/SASH1 Autoregulatory Feedback Loop Activates Mutated SASH1 to Cause Pathologic Hyperpigmentation" by Ding'an Zhou, Jiawei Zeng, Pingshen Hu, and Xiaodong Su, the authors focus on the

promising oncotheranostics strategy.

treatments for ovarian cancer patients.

pathological conditions.

specificity.

bioapplications.

**1**

**2. OMICS technology**

**Chapter 1**

**1. Introduction**

Introductory Chapter: Insight

Molecular Medicine

of the whole genome with the environment [2].

strategies and their emerging roles in biomedical research.

*Sinem Nalbantoglu and Abdullah Karadag*

into the OMICS Technologies and

Molecular medicine aims to reveal molecules, such as genes, transcripts, proteins, and metabolites, to underlie the mechanism behind the physicological processes as well as alterations during the pathological conditions at the cellular level. Furthermore, molecular medicine intends to improve public healthcare and disease management through development of biomarker-based screening, diagnostic, and monitoring systems as well as target- and mechanism-based treatment strategies. Human Genome Project has been completed in 2003, exactly 50 years after Watson and Crick invented DNA structure. Based on this valuable breakthrough, the twenty-first century's molecular medicine approaches have been attributed to identify and understand functions and interactions of human genes to shed further light on health and disease mechanisms at the basic molecular and cellular level. Published by James Watson in the first edition of "The Molecular Biology of the Gene" (1965), the central dogma of molecular biology was a complete demonstration of the flow of genetic information basically described as DNA makes RNA, which in turn makes proteins: DNA → RNA → protein [1]. However, later on the 1980s–1990s by applying improved molecular biology methods, the single gene and inheritance concept has changed to multiple genes and inheritance with interactions of genes, RNAs, proteins, and environment in a particular cell. Extinction of central dogma has led to proper and critical understanding of diseases and generation of molecular medicine. By this way, a new concept called phenome, as the total phenotypic characteristics of an organism, has emerged, which implies interaction

Primary objectives of molecular medicine includes predicting potential future pathologies, identifying disease state through effective screening and early diagnosis systems, decision on effective treatment strategies, monitoring the prognosis and health care, and predicting recurrence earlier to apply alternative treatments. In this regard, molecular medicine aims to obtain decreased under/over/mis-diagnosis and generate effective targeted therapies without side effects. Here, we provide an overview of the latest headings of molecular medicine including promising research

The terms "Ome" derived from a Greek word and "Omics" are derivations of the suffix -ome which means "whole," "all," or "complete." With the addition of -ome to

### **Chapter 1**
