Precision Medicine in Oncology

Bulent Aydogan, James A. Radosevich, Bulent Aydogan, James A. Radosevich

• Publisher: Wiley-Blackwell
• Year: 2020
• Print ISBN:
  9781119432449
• eBook ISBN:
  9781119432494
• Edition: 1
• Topic: Medicine
• Subtopic: Oncology

A FRESH EXAMINATION OF PRECISION MEDICINE'S INCREASINGLY PROMINENT ROLE IN THE FIELD OF ONCOLOGY

Precision medicine takes into account each patient's specific characteristics and requirements to arrive at treatment plans that are optimized towards the best possible outcome. As the field of oncology continues to advance, this tailored approach is becoming more and more prevalent, channelling data on genomics, proteomics, metabolomics and other areas into new and innovative methods of practice. Precision Medicine in Oncology draws together the essential research driving the field forward, providing oncology clinicians and trainees alike with an illuminating overview of the technology and thinking behind the breakthroughs currently being made.

Topics covered include:

• Biologically-guided radiation therapy
• Informatics for precision medicine
• Molecular imaging
• Biomarkers for treatment assessment
• Big data
• Nanoplatforms

Casting a spotlight on this emerging knowledge base and its impact upon the management of tumors, Precision Medicine in Oncology opens up new possibilities and ways of working – not only for oncologists, but also for molecular biologists, radiologists, medical geneticists, and others.

1
Genomic Strategies for Personalized Cancer Therapy

Arkadiusz Z. Dudek^1,2, Kate Baxstrom², Sushma Bharadwaj³, Anne Blaes², Amit Kulkarni², Emil Lou², Vijeyaluxmy Nehru⁴, Emma Rabinovich⁴, Ardaman Shergill⁴, and Maya Viner⁴

¹ HealthPartners Cancer Care Center, St. Paul, MN, USA

² University of Minnesota, Minneapolis, MN, USA

³ Rush Medical College, Chicago, IL, USA

⁴ University of Illinois at Chicago, Chicago, IL, USA

1.1 Introduction

1.1.1 Definition of Precision Medicine in Oncology

In cancer therapy, the initial development effort was on empiric discovery of cancer therapeutics through a search of agents toxic against cancer cell lines. With a better understanding of cancer biology, there was identification of specific cancer targets, such as hormone receptors (HR) (estrogen, progesterone, androgen), human epidermal growth factor family receptors (HER2, EGFR), vascular endothelial growth factor (VEGF) receptors, and others. Perhaps the history of development of epidermal growth factor receptor (EGFR)‐targeted therapy best exemplifies challenges on how to maximize the effects of targeted therapy. Initially, EGFR‐targeted agents, such as gefitinib and erlotinib, were used as therapy for all non‐small cell lung cancer (NSCLC) patients, resulting in only a small proportion of patients benefiting from that therapy. Several years later was there a realization that only individuals with lung cancer tumors with mutated EGFR protein had remarkable responses.

The goal of precision oncology is to understand the molecular mechanisms of cancer formation, and an individual's unique characteristics, in order to maximize therapeutic response and minimize treatment side effects. This can be accomplished by discovery of driver oncogenic pathways in the tumor of an individual, with a set of genetic and protein expression assays, and then directing a specific cancer agent against these pathways to maximize therapeutic response. In addition, there is a parallel effort to understand features about the host to understand an individual's unique drug metabolism or immune status to optimize anticancer effect and minimize toxicity.

The following sections describe methods used for precision oncology, recent advances in genome‐guided treatment of selected malignancies, challenges in development of biomarkers, precision oncology clinical trial design, and ethical and technological issues ahead in this era of precision medicine in oncology.

1.1.2 DNA and RNA Sequencing Techniques

Over the past decade, molecular biology methods and techniques have become increasingly sophisticated, well‐validated, and reliable, as well as more affordable and widespread. The application of precision genomics is still relatively early to the field of medical oncology, and is very much evolving. The ultimate goal is to achieve a true ability to tailor treatments for each individual patient, in real time, as their tumor(s) evolve during the course of drug treatment, as compared to the traditional paradigm of treating classes of patients based on the tissue site of origin of their malignancies [1]. Here, we will provide a general overview of the current landscape of assays and techniques in routine clinical use.

Many platforms have been and remain under investigation, and even those that have been widely adopted continue to be refined to improve accuracy and speed of output. Genomic platforms for precision oncology include tumor‐based and blood‐based assays, and techniques that target assessment of DNA (deoxyribonucleic acid) and/or RNA (ribonucleic acid) at the genetic level. Sequencing of DNA focuses on identification of potential actionable, or drug targetable, mutations, translocations, and amplifications or gains (involving heterozygous or homozygous deletions) [1]. The methods used include targeted next‐generation sequencing (NGS) as well as traditional Sanger sequencing to identify pertinent mutations. Polymerase chain reaction (PCR) is used to determine gene dosage that can vary in amplified regions of DNA [1]. For sites of DNA translocation, while immunohistochemistry (IHC) has been the more traditional standard of identification and validation, use of fluorescence in situ hybridization (FISH) is used more commonly to improve accuracy of detection. A technique that has increased in usage over the past decade is comparative genomic hybridization (CGH), which has especially gained favor for assessing copy number alterations [2]. CGH is used in large‐scale, genomically driven basket clinical trials in Europe (e.g. molecularly targeted therapy based on tumor molecular profiling versus conventional therapy for advanced cancer [SHIVA] [2]) and in the United States. Most prominently, the National Cancer Institute’s Molecular Analysis for Therapy Choice (NCI‐MATCH) trial [3], has used this method in completed portions or ongoing parts of these trial studies. As an example of accuracy of assessment, in NCI‐MATCH, the use of NGS achieved a high sensitivity (~96.7%) and specificity (99.9%) [3]. This ability was also found to be highly reproducible across multiple sites (four centers, in the referenced analysis), providing strong support to the notion that basket trials can be done reliably on a wide‐scale basis with confidence based on accurate NGS reporting. However, what will be critical in the years to come is the determination of whether smaller to mid‐level centers will have the resources to invest in building NGS platforms that can live up to this standard, or whether larger centers will become central clearinghouses for testing of samples sent from o...

Table of contents

• Cover
• Table of Contents
• Title Page
• Copyright Page
• List of Contributors
• Preface
• List of Abbreviations
• 1 Genomic Strategies for Personalized Cancer Therapy
• 2 Blood‐Based Biomarkers for the Diagnosis and Prognosis of Cancer
• 3 Application of Circulating Cell‐free DNA for Personalized Cancer Therapy
• 4 Prognostic Implications of EGFR, p53, p16, Cyclin D1, and Bcl‐2 in Head and Neck Squamous Cell Carcinoma (HNSCC)
• 5 Immunotherapy and Cancer
• 6 Predictive and Prognostic Markers for Cancer Medicine
• 7 Dual Energy Imaging in Precision Radiation Therapy
• 8 The Role of Big Data in Personalized Medicine
• Index
• End User License Agreement