Progress and Challenges in Precision Medicine

Mukesh Verma, Debmalya Barh

• Publisher: Academic Press
• Year: 2016
• Print ISBN: 9780128094112
• eBook ISBN: 9780128095027
• Topic: Biological Sciences
• Subtopic: Genetics & Genomics
• Index: Biological Sciences

Progress and Challenges in Precision Medicine presents an insightful overview to the myriad factors of personalized and precision medicine. The availability of the human genome, large amounts of data on individual genetic variations, environmental interactions, influence of lifestyle, and cutting-edge tools and technologies for big-data analysis have led to the age of personalized and precision medicine. Bringing together a global range of experts on precision medicine, this book collects previously scattered information into one concise volume which covers the most important developments so far in precision medicine and also suggests the most likely avenues for future development. The book includes clinical information, informatics, public policy implications, and information on case studies. It is a useful reference and background work for students, researchers, and clinicians working in the biomedical and medical fields, as well as policymakers in the health sciences. - Provides an overview of the growing field of precision medicine - Contains chapters from geographically diverse experts in their field - Explores important aspects of precision medicine, including applications, ethics, and development

Chapter 1

Introduction

Every Individual Is Different and Precision Medicine Offers Options for Disease Control and Treatment

C. Hizel^1,2, J. Tremblay^1,2,3,4, G. Bartlett⁵, and P. Hamet^{2,3,6 1}OPTI-THERA, Montreal, QC, Canada ²International and Interdisciplinary Association on the Pharmaceutical Life Cycle (AIICM/IIAPC), Montréal, QC, Canada ³Université de Montréal, Montréal, QC, Canada ⁴CRCHUM, Montreal, QC, Canada ⁵McGill University, Montreal, QC, Canada ⁶CHUM, Montreal, QC, Canada

Abstract

With the availability of high-throughput genomics technologies and the completion of the Human Genome Project in 2003, we are now in the “postgenomics era.” The concept of precision medicine evolved over time and was popularized only recently. It became a hot topic in the medical community as well as in public sphere due to president Obama's announcement of the “Precision Medicine Initiative” at the beginning of 2015. In principle, the term “precision medicine” referring to multiple omics profiles, which include genomics, pharmacogenomics, proteomics, metabolomics, transcriptomics, epigenomics, and metagenomics, takes into account family history and lifestyles to make more tailored diagnostic and therapeutic strategies to a particular patient with different monogenic and multifactorial polygenic complex diseases, such as diabetes. The term “personalized medicine” is wider, more inclusive of subjects' environment, exposure, and socioeconomic status. However, besides technical issues, as a cornerstone of individual approach, precision medicine can fulfill its promise and build its sustainable existence by addressing and asking precision questions regarding structural deficiencies in health care system for the most vulnerable patients and pathologies including neglected diseases and global epidemic of complex noncommunicable diseases, such as diabetes in the society of not only high-income but also in low- and middle-income countries.

Keywords

Diabetes; Low- and middle-income countries (LMICs); Noncommunicable diseases (CNCDs); Omics; Precision medicine

1. What Is Precision Medicine? Personalized Medicine Versus Precision Medicine (C. HIzel, P. Hamet, and J. Tremblay)

The push to appeal precision medicine for patient health care as individual approach received a major boost with the announcement of a $215 million for “Precision Medicine Initiative” by President Obama earlier on January 2015 (www.whitehouse.gov/precision-medicine). There is a lot of overlap between the terms “Precision” and “personalized” medicine and sometimes are used interchangeably with very subtle difference in life sciences. The more popularized term “precision medicine,” emphasizes more the stratification of molecular-level information, whereas “personalized medicine” is more defined with the ability to tailor treatments, as well as prevention strategies, to the unique characteristics of each person (Jameson and Longo, 2015; Mirnezami et al., 2012).

Even if with both terms genomic studies are one of the principal components for identifying the “Achilles heel” of the subject affected by the disease, it is only one piece of the puzzle. Thereby, the creation of robust data from genomic risk to the “exposome” together with medical histories, social factors, and lifestyle factors is pivotal and they cannot act in isolation, but in concert to fulfill prior engagement of both terms (personalized/precision) in drug effectiveness and safety as much as in susceptibility to common multifactorial complex diseases for more precise personalized health care (Pashayan et al., 2011; Kittles, 2012). Like personalized medicine, precision medicine is neither parallel nor perpendicular! This is a highly interactive field that requires a synthesis in medicine, biochemistry, molecular biology, genetics, and even sociology and politics making a call to the informatics and biostatistics. That is to say, it is a matter of interdisciplinarity. Since the completion of Human Genome Project in 2003 symbolically announced the postgenomic era, determining the precise molecular structure of DNA and understanding the genome structure revolutionized our concept of health due to rapid development of molecular medicine specifically genetics, informatics, and other high-throughput technologies (e.g., nanotechnology, proteomics, metabolomics) which has led scientists and physicians to have an avant-garde thinking about how to detect and finally treat disease precisely (Naidoo et al., 2011). Upon the arrival of “postgenomics” era medicine with the completion of the Human Genome Project (HGP) in 2003, an important conceptual shift is done on “prediction/prevention” of future health outcomes (e.g., disease susceptibility, response to health interventions) with the use of individual genetic/genomics information. A corollary is that preventive and customized interventions and diagnostic tests may now be conceptualized (and in some cases implemented) during the presymptomatic phase of a disease or before pharmacotherapy is initiated (Hizel et al., 2009; Aydin Son et al., 2013). The concept of prevention represents the next step in the development of the “predictive medicine” as conceived by Jean Dausset, one of the three winners of the Nobel Prize in Physiology/Medicine in 1980. Dausset has suggested the term “predictive medicine” as a prerequisite step for preventive medicine. Subsequently in 1993, Jacques Ruffie offered a more comprehensive definition for the term and laid the philosophical basis for this new field in a book entitled “Naissance de la Médecine Prédictive” (Birth of Predictive Medicine) (Ruffié, 1993). Today, the term “predictive medicine” is replaced by one that is more precise: “personalized medicine” and “precision medicine” enabled by the introduction and availability of high-throughput genomics technologies (Hizel et al., 2009; Aydin Son et al., 2013). As a consequence of genetic diversity and the existence of our genes in different forms in different environments with different lifestyles, the genetic basis of individual approach is resumed as “we are all different,” which reflects the presence of genetic diversity (Cavalli-Sforza and Piazza, 1993; Cavalli-Sforza, 1997). Behind this expression, there is a scientific phenomenon called polymorphism. Our genes exist in different forms which determine the differences in “gene activity.” More than 93% of genes are polymorphic such as single nucleotide polymorphism (SNP) (Chakravarti, 2001). Polymorphism, especially SNP has the power to predict enzyme activity encoded by this or that gene. SNP detection enables us to understand better metabolic peculiarities in each case (Lai, 2001). So, precision medicine as a part of new genetics (Sutton, 1995) is based on the polymorphism phenomenon which now can be applied even in routine medical practice. In the light of new knowledge from genome studies and their by-products, matching molecular and genetic profiling with clinical–pathological data is important to create precise individual approach in disease predisposition (“who is at risk”), diagnosis (“what is the cause”), prognostic (“who to treat”), therapeutic response (“how to treat”) as treatment decision-making and prevention strategies in day-to-day personalized health care (Ginsburg and McCarthy, 2001; McCarthy et al., 2013). However, the activity of enzymes is not only under the control of genetic factors but also environmental factors which change gene activity–gene expression leading to different phenotypic expression for different diseases. Cells and tissue are in continuous communication across different interacting layers, such as DNA, RNA, and protein to maintain homeostasis and regulate biological processes in response to external environmental stimuli (Hausman et al., 2009). Accordingly, the main principle for the development of predictive and personalized/precision medicine as presented in Fig. 1.1, all of us “as open system” are the result of constant communication between our genes an...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• List of Contributors
• Biography
• Dedication
• Preface
• Chapter 1. Introduction: Every Individual Is Different and Precision Medicine Offers Options for Disease Control and Treatment
• Chapter 2. Clinical Next-Generation Sequencing: Enabling Precision Medicine
• Chapter 3. Phenotyping in Precision Medicine
• Chapter 4. Cancer Genetic Screening and Ethical Considerations for Precision Medicine
• Chapter 5. Precision Medicine in Primary Health Care
• Chapter 6. Population Approach to Precision Medicine
• Chapter 7. Regulation of Genomic Testing in the Era of Precision Medicine
• Chapter 8. Image-Based Modeling and Precision Medicine
• Chapter 9. Sharing Outside the Sandbox? The Child’s Right to an Open Data Sharing Future in Genomics and Personalized Medicine
• Chapter 10. Lessons Learned From Cohort Studies, and Hospital-Based Studies and Their Implications in Precision Medicine
• Chapter 11. Clinical Trials in Precision Medicine
• Chapter 12. Time to Educate Physicians and Hospital Staff in Electronic Medical Records for Precision Medicine
• Chapter 13. Computational Approaches in Precision Medicine
• Chapter 14. Handling Big Data in Precision Medicine
• Chapter 15. Trends in Precision Medicine
• Chapter 16. Personalized Medicine: Interdisciplinary Perspective, World Tidal Wave, and Potential Growth for the Emerging Countries
• Index