Biomarker Tests For Molecularly Targeted Therapies

Every patient is unique, and the evolving field of precision medicine aims to ensure the delivery of the right treatment to the right patient at the right time. In an era of rapid advances in biomedicine and enhanced understanding of the genetic basis of disease, health care providers increasingly have access to advanced technologies that may identify molecular variations specific to an individual patient, which subsequently can be targeted for treatment. Known as biomarker tests for molecularly targeted therapies, these complex tests have the potential to enable the selection of the most beneficial treatment (and also to identify treatments that may be harmful or ineffective) for the molecular underpinnings of an individual patient's disease. Such tests are key to unlocking the promise of precision medicine. Biomarker tests for molecularly targeted therapies represent a crucial area of focus for developing methods that could later be applicable to other areas of precision medicine. The appropriate regulatory oversight of these tests is required to ensure that they are accurate, reliable, properly validated, and appropriately implemented in clinical practice. Moreover, common evidentiary standards for assessing the beneficial impact of biomarker-guided therapy selection on patient outcomes, as well as the effective collection and sharing of information related to those outcomes, are urgently needed to better inform clinical decision making. Biomarker Tests of Molecularly Targeted Therapies examines opportunities for and challenges to the use of biomarker tests to select optimal therapy and offers recommendations to accelerate progress in this field. This report explores regulatory issues, reimbursement issues, and clinical practice issues related to the clinical development and use of biomarker tests for targeting therapies to patients. Properly validated, appropriately implemented biomarker tests hold the potential to enhance patient care and improve outcomes, and therefore addressing the challenges facing such tests is critical.

A long-held goal in oncology has been to develop therapies that target the specific abnormalities in each patient's cancer rather than simply treating cancers based on the tissue of origin. In the past decade, advances in technology have enabled researchers to relatively quickly and inexpensively determine, in minute detail, the genetic makeup of tumors. Although relatively few targeted cancer therapies are currently available in the clinic and it is not yet clear whether all cancers are driven by genetic changes that can be targeted, there is widespread optimism in the cancer community that this new ability to assess the genetic abnormalities in tumors will ultimately lead to better cancer treatments and improved patient outcomes. Policy Issues in the Development and Adoption of Biomarkers for Molecularly Targeted Cancer Therapies is the summary of a workshop convened in November 2014 by the Institute of Medicine's National Cancer Policy Forum to discuss recent trends in the development and implementation of molecularly targeted cancer therapies and explore potential policy actions to address specific challenges. This report highlights the presentations and discussions at the workshop.

“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.

Research has long sought to identify biomarkers that could detect cancer at an early stage, or predict the optimal cancer therapy for specific patients. Fueling interest in this research are recent technological advances in genomics, proteomics, and metabolomics that can enable researchers to capture the molecular fingerprints of specific cancers and fine-tune their classification according to the molecular defects they harbor. The discovery and development of new markers of cancer could potentially improve cancer screening, diagnosis, and treatment. Given the potential impact cancer biomarkers could have on the cost effectiveness of cancer detection and treatment, they could profoundly alter the economic burden of cancer as well. Despite the promise of cancer biomarkers, few biomarker-based cancer tests have entered the market, and the translation of research findings on cancer biomarkers into clinically useful tests seems to be lagging. This is perhaps not surprising given the technical, financial, regulatory, and social challenges linked to the discovery, development, validation, and incorporation of biomarker tests into clinical practice. To explore those challenges and ways to overcome them, the National Cancer Policy Forum held the conference "Developing Biomarker-Based Tools for Cancer Screening, Diagnosis and Treatment: The State of the Science, Evaluation, Implementation, and Economics" in Washington, D.C., from March 20 to 22, 2006. At this conference, experts gave presentations in one of six sessions. In addition, seven small group discussions explored the policy implications surrounding biomarker development and adoption into clinical practice. Developing Biomarker-based Tools for Developing Cancer Screening, Diagnosis, and Treatment: The State of the Science, Evaluation, Implementation, and Economics-Workshop Summary presents the conference proceedings and will be used by an Institute of Medicine (IOM) committee to develop consensus-based recommendations for moving the field of cancer biomarkers forward.

Technologies collectively called omics enable simultaneous measurement of an enormous number of biomolecules; for example, genomics investigates thousands of DNA sequences, and proteomics examines large numbers of proteins. Scientists are using these technologies to develop innovative tests to detect disease and to predict a patient's likelihood of responding to specific drugs. Following a recent case involving premature use of omics-based tests in cancer clinical trials at Duke University, the NCI requested that the IOM establish a committee to recommend ways to strengthen omics-based test development and evaluation. This report identifies best practices to enhance development, evaluation, and translation of omics-based tests while simultaneously reinforcing steps to ensure that these tests are appropriately assessed for scientific validity before they are used to guide patient treatment in clinical trials.

Discover how biomarkers can boost the success rate of drug development efforts As pharmaceutical companies struggle to improve the success rate and cost-effectiveness of the drug development process, biomarkers have emerged as a valuable tool. This book synthesizes and reviews the latest efforts to identify, develop, and integrate biomarkers as a key strategy in translational medicine and the drug development process. Filled with case studies, the book demonstrates how biomarkers can improve drug development timelines, lower costs, facilitate better compound selection, reduce late-stage attrition, and open the door to personalized medicine. Biomarkers in Drug Development is divided into eight parts: Part One offers an overview of biomarkers and their role in drug development. Part Two highlights important technologies to help researchers identify new biomarkers. Part Three examines the characterization and validation process for both drugs and diagnostics, and provides practical advice on appropriate statistical methods to ensure that biomarkers fulfill their intended purpose. Parts Four through Six examine the application of biomarkers in discovery, preclinical safety assessment, clinical trials, and translational medicine. Part Seven focuses on lessons learned and the practical aspects of implementing biomarkers in drug development programs. Part Eight explores future trends and issues, including data integration, personalized medicine, and ethical concerns. Each of the thirty-eight chapters was contributed by one or more leading experts, including scientists from biotechnology and pharmaceutical firms, academia, and the U.S. Food and Drug Administration. Their contributions offer pharmaceutical and clinical researchers the most up-to-date understanding of the strategies used for and applications of biomarkers in drug development.

This book reviews the current applications of molecular tools in cytopathology and provides a concise handbook for those who provide care in this era of personalized medicine. Specifically, the text provides a comprehensive and concise review of the emerging molecular tests available clinically in different subspecialities of diagnostic pathology. It reviews the current data of molecular testing already applied in cytopathology, discusses some of the biomarkers with potential utility in cytopathology in the near future and reviews the technical challenges in applying and validating molecular tools in liquid-based cytologic materials. Molecular Cytopathology will serve as a valuable resource for cytopathologists, cytotechnologists, pathology trainees, and clinicians with an interest in molecular applications in cytopathology.