Introduction to Predictive Biomarkers: definitions and characteristics.- Introduction to clinical trials, clinical trial designs and statistical terminology used for predictive biomarker research and validation.- Overview of Methods Used in Predictive Biomarker Studies in a Molecular Anatomic Pathology Laboratory.- Significance of Immunohistochemistry and In Situ Hybridization Techniques for Predictive Biomarker Studies.- Overview of PCR-based Technologies and Multiplexed Gene Analysis for Biomarker Studies.- Introduction to Microarray Technology.- Digital and Computational Pathology for Biomarker Discovery.- Detection of Predictive Biomarkers Using Liquid Biopsies.- Measurement of Predictive Cancer Biomarkers by Flow Cytometry.- Personalized Cancer Treatment and Patient Stratification Using Massive Parallel Sequencing (MPS) and Other OMICs Data.- Bioinformatic Methods and Resources for Biomarker Discovery, Validation, Development, and Integration.- Overview of Cell Signaling Pathways in Cancer.- Steroid Hormone and Nuclear Receptor signaling pathways.- Protein kinase C Signaling in Carcinogenesis.- Roles of Rho/ROCK in Cancer Signaling.- Mitogen Activated Protein Kinase (MAPK) Signaling.- Notch Signaling Pathway in Carcinogenesis.- Signaling of the ErbB receptor Family in Carcinogenesis and the Development of Targeted Therapies.- Signaling Pathways in Tumor Angiogenesis and Anti-angiogenic Therapies in Human Cancer.- Role of PI3K/AKT/mTOR in Cancer Signaling.- Met Signaling in Carcinogenesis.- Role of Insulin-like Growth Factor Receptors in Cancer Signaling.- Role of Wnt/ss-catenin Pathway in Cancer Signaling.- Hedgehog Signaling in Carcinogenesis.- TGF-ss and the SMAD Signaling Pathway in Carcinogenesis.- Role of JAK-STAT Pathway in Cancer Signaling.- NF-kB signaling pathways in Carcinogenesis.- Immune-Signaling in Carcinogenesis.- Predictive Biomarkers and Targeted Therapies in Immuno-Oncology.- Role of Protein Tyrosine Phosphatases in Cancer Signaling.- Predictive and Prognostic Biomarkers in Myeloid Neoplasms.- Predictive Biomarkers and Targeted Therapies for Lymphoid Malignancies.- Targeted Therapies for Pediatric Central Nervous System Tumors.- Predictive Biomarkers and Targeted Therapies in Adult Brain Cancers.- Predictive Biomarkers and Targeted Therapies in Breast Cancer.- Predictive Biomarkers in Lung Cancer.- Predictive Biomarkers and Targeted Therapies in Genitourinary Cancers.- Predictive Biomarkers and Targeted Therapies in Colorectal Cancer.- Predictive Markers and Targeted Therapies in Gastroesophageal Cancer (GEC).- Predictive Biomarkers and Targeted Therapies in Hepatic, Pancreatic, and Biliary Cancers .- Gynecological Cancers & Head and Neck Cancers.- Predictive Biomarkers and Targeted Therapies in Head and Neck Cancer.- Predictive Biomarkers and Targeted Therapies in the Skin.- Predictive Biomarkers and Targeted Therapies in Sarcomas.- Predictive Markers and Targeted Therapies in Thyroid Cancer and Selected Endocrine Tumors.- The Response Evaluation Criteria in Solid Tumors (RECIST).- IVDs and FDA Marketing Authorizations: A General Overview of FDA Approval Process of an IVD Companion Diagnostic Device in Oncology.- Quality Control of Immunohistochemical and In Situ hybridization Predictive Biomarkers for Patient Treatment: Experience from International Guidelines and International Quality Control Schemes.- Use of Companion Diagnostics (CDx) and Predictive Biomarkers for Cancer Targeted Therapy. Clinical Applications in Precision Medicine.- Policy issues in the clinical development and use of predictive biomarkers for molecular targeted therapies.- Role of central laboratories in research, validation and application of predictive biomarkers.- Prominent Precision Medicine Clinical Trials in Oncology Around the World.- Precision Medicine Clinical Trials: Successes and Disappointments, Challenges and Opportunities. Lessons Learnt.- FDA Approved Targeted Therapies in Oncology.
"Precision/personalized or stratified medicine" refers to the tailoring of medical treatment or drug administration to the individual characteristics of each patient treatment. It does not literally mean that a pharmaceutical company makes a drug for an individual patient for consumption and treatment but rather means the ability to stratify (or classify) individuals into sub-populations that differ in their responsiveness to a specific drug. A marker that provides information on the likely response to therapy, i.e., either in terms of tumor shrinkage or survival of the patient is termed "predictive biomarker". Despite their promise in precision medicine and the explosion of knowledge in this area, there is not a single source on this subject that puts all this evidence together in a concise or richly illustrated and easy to understand manner.
This book provides a collection of ingeniously organized, well-illustrated and up-to-date authoritative chapters divided into five sections that are clear and easy to understand. Section one provides an overview of biomarkers, introduces the basic terminologies, definitions, technologies, tools and concepts associated with this subject in the form of illustrations/graphics, photographs and concise texts. Several recent biomarker endeavors that have been initiated and funded by the National Cancer Institute, National Institutes of Health, FDA and other International organizations are presented. Section two involves the signaling pathways controlling cell growth and differentiation altered in cancer. This section analyzes how predictive biomarkers are altered (expressed or amplified) across cancer types. Section three explores how predictive biomarkers play a role in patient stratification and tailored treatment in relationship to specific cancers. In addition, it includes discussion on the various precision medicine initiatives that are going on across the globe (e.g. TARGET, NCI-MATCH, BATTLE, SHIVA, etc.). Section four discusses: (a) how pharmaceutical companies validate predictive biomarker assays and accompanying companion diagnostics either internally or externally with partner companies such as central laboratories or clinical research organizations, and (b) how predictive biomarker tests fall under the oversight of US FDA, Centers for Medicare & Medicaid Services (CMS) and state laws. Section five wraps up novel agents and targets that are being used as targets for cancer therapeutics. The biomarkers associated with these protocols will also be presented. Throughout the book, sidebars, special interest boxes and illustrations are used to explain terms that are either newly introduced, uncommon, or specialized.
Predictive Biomarkers in Oncology will serve as a definitive guide for practicing pathologists, oncologists, basic researchers, and personnel in the pharmaceutical or diagnostic industry interested in learning how "predictive biomarkers" are used in precision cancer therapy.
Sunil Badve, Indiana University School of Medicine, Indianapolis, IN, USA
George Kumar, Targos Inc., Issaquah, WA, USA