Biomarkers in Cancer Screening and Early Detection

Prepared by world leaders on this topic, Biomarkers in Cancer Screening and Early Detection offers a comprehensive, state-of-the-art perspective on the various research and clinical aspects of cancer biomarkers, from their discovery and development to their validation, clinical utility, and use in developing personalized cancer treatment.

• Offers a comprehensive, state-of-the-art perspective on the various research and clinical aspects of cancer biomarkers
• Provides immediately actionable information – and hopefully also inspiration – to move discovery and clinical application forward
• Offers vital knowledge to help develop personalized cancer treatment for individual patients with specific cancers

List of Contributors, ix

Preface, xiii

Part I Foundations of Biomarker Research

1 Nuts and Bolts of Biomarker Research, 3
Sharmistha Ghosh and Sudhir Srivastava

2 Cancer Genome Methylation: Biology, Biomarker and Therapeutic Opportunities, 16
Shashwat Sharad, Taduru Sreenath, Shiv Srivastava, and Albert Dobi

3 MicroRNA Biomarkers for Early Detection of Cancer, 27
WendyWang, Matthew R Young, and Sudhir Srivastava

4 Inflammation and Cancer, 37
Pamela L Beatty, Sandra Cascio, and Olivera J Finn

5 Exosomes: A Valuable Biomedical Tool in Biomarker Discovery and Development, 50
Jocelyn Lee, Sharmistha Ghosh, and Sudhir Srivastava

6 Epithelial-to-Mesenchymal Transition (EMT): Clinical Implications, 64
Elisa CWoodhouse and Suresh Mohla

Part II State-of-the-Science in Organ-Specific Biomarker Research

7 Breast Cancer, 77
Benjamin A Katchman, Christos Patriotis, and Karen S Anderson

8 Ovarian Cancer, 93
Christos Patriotis, Archana Simmons, Karen H Lu, Robert C Bast, Jr, and Steven J Skates

9 Esophageal Cancer Biomarkers, 104
Yanxin Luo, Kishore Guda, SanfordD Markowitz, Amitabh Chak, Andrew M Kaz, andWilliam M Grady

10 Predictive Biomarkers for Therapy in Adenocarcinoma of the Upper Digestive Tract, 118
Heath D Skinner, Qiongrong Chen, Elena Elimova, RoopmaWadhwa, Shumei Song, and Jaffer A Ajani

11 Pancreatic Cancer, 130
Sam CWang and Peter J Allen

12 Colon Cancer, 141
Paul DWagner

13 Prognostic and Predictive Biomarkers for Colorectal Cancer, 151
Upender Manne, Balananda-Dhurjati Kumar Putcha, Temesgen Samuel, and Sudhir Srivastava

14 Early Detection of Lung Cancer, 163
Mohamed Hassanein, Melinda C Aldrich, Stephen A Deppen, Karl E Krueger, Eric L Grogan, and Pierre P Massion

15 Commonalities in Lung Cancer and COPD, 185
MalgorzataWojtowicz and Eva Szabo

16 Prostate Cancer, 197
Jacob Kagan, Ian M Thompson, and DanielWChan

Part III Biomarkers, Screening and Precision Health: Implications for Public Health

17 Improving the Clinical Validity of Biomarker Research in Cancer Detection, 209
David F Ransohoff

18 Cancer Overdiagnosis, Ramifications and Research Strategies, 220
Barbara K Dunn and Barnett S Kramer

19 Predictive Markers and Driver Genes From Treatment Trials: Potential Utility For Early Diagnosis, 231
Brian S Sorg, Sarfraz Memon, Kelly Y Kim, Aniruddha Ganguly, Tracy Lively, James Tricoli, Magdalena Thurin, Lokesh Agrawal, Tawnya C McKee, Barbara A Conley, and J Milburn Jessup

20 Statistical Consideration in Predictive and Prognostic Markers, 245
Fei Ye and Yu Shyr

21 Clinical Validation of Molecular Biomarkers in Translational Medicine, 256
Harry B Burke and William E Grizzle

22 Cancer Biomarker Assays: Performance Standards, 267
Anna K Fuzery and Daniel W Chan

23 Bioethics and Cancer Biomarker Research, 277
Nathan Nobis, William Grizzle, and Stephen Sodeke

24 Colon Cancer Screening, 283
Molly Perencevich, Jennifer Inra, and Sapna Syngal

Edited by
Sudhir Srivastava, Ph.D., MPH Senior Scientific Officer, Chief, Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

Translational Oncology Series
Series Editors
ROBERT C. BAST, MD, Vice President for Translational Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

MAURIE MARKMAN, MD, Senior Vice President for Clinical Affairs, Cancer Treatment Centers of America, Clinical Professor of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA

ERNEST HAWK, MD, MPH, Vice President, Division of OVP, Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Biomarkers in Cancer Screening and Early Detection offers a comprehensive, state-of-the-art perspective on the various research and clinical aspects of cancer biomarkers, from their discovery and development to their validation, clinical utility, and clinical use. The primary purpose of this book is to summarize and present best practices in this field to date, and offer actionable information – and hopefully also inspiration – to move discovery and clinical application forward.

This latest volume of the Translational Oncology series, Biomarkers in Cancer Screening and Early Detection is organized into three sections: Section I lays the foundation for biomarker discovery, development and validation. Section II presents organ-specific topics relevant to the clinical needs in early detection, the natural history of the disease and associated evidence in support of biomarker research, an overview of the current state-of-the art in biomarker research, current progress toward bringing these biomarkers into clinical use and the future of biomarker-based screening and early detection for the respective organ type. Finally, Section III offers chapters that address the current screening strategies for selected organ types, discuss deficiencies with the present practice and identify clinical needs that may benefit from biomarker-based approaches.

This latest volume of the Translational Oncology series, Biomarkers in Cancer Screening and Early Detection:

• Provides immediately actionable information – and hopefully also inspiration – to move discovery and clinical application forward
• Considers the cutting edge "bench to bedside and back" breakthroughs which have transformed the diagnosis, prognosis and treatment of cancer
• Discusses screening guidelines, research strategies, and issues surrounding cancer overdiagnosis
• Offers vital knowledge to help develop personalized cancer treatment for individual patients with specific cancers



The development of cancer is preceded by numerous mutations and changes which transform normal cells into benign tumors, and progressively into malignant and metastatic forms. This enormous complexity makes cancer detection, diagnosis, and treatment challenging and therefore the ability to identify tumors that are destined to progress at an early stage will allow effective treatment interventions and reduce deaths. This new book comprehensively summarises the current state of play and is an ideal resource for clinical and research oncologists interested in the progress of screening and detection of cancer.