Cancer Theranostics

Xiaoyuan Chen, Stephen Wong

• Publisher: Academic Press
• Year: 2014
• ISBN:
  9780124078840
• Topic: Medicine
• Subtopic: Oncology

Aiding researchers seeking to eliminate multi-step procedures, reduce delays in treatment and ease patient care, Cancer Theranostics reviews, assesses, and makes pertinent clinical recommendations on the integration of comprehensive in vitro diagnostics, in vivo molecular imaging, and individualized treatments towards the personalization of cancer treatment.

Cancer Theranostics describes the identification of novel biomarkers to advance molecular diagnostics of cancer. The book encompasses new molecular imaging probes and techniques for early detection of cancer, and describes molecular imaging-guided cancer therapy. Discussion also includes nanoplatforms incorporating both cancer imaging and therapeutic components, as well as clinical translation and future perspectives.

• Supports elimination of multi-step approaches and reduces delays in treatments through combinatorial diagnosis and therapy
• Fully assesses cancer theranostics across the emergent field, with discussion of biomarkers, molecular imaging, imaging guided therapy, nanotechnology, and personalized medicine
• Content bridges laboratory, clinic, and biotechnology industries to advance biomedical science and improve patient management

Part I

In Vitro Diagnostics

Outline

Chapter 1 Cancer Theranostics: An Introduction

Chapter 2 Genomics-Based Cancer Theranostics

Chapter 3 Proteomics-Based Theranostics

Chapter 1

Cancer Theranostics

An Introduction

Xiaoyuan Chen* and Stephen T.C. Wong^†, ^*Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, U.S.A., ^†Department of Systems Medicine and Bioengineering, Houston Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, Texas, U.S.A.

Cancer theranostics combines cancer diagnosis and cancer therapy, aiming for early diagnosis, accurate molecular imaging, and precise treatment at the right timing and proper dose, followed by real-time monitoring of treatment efficacy. This chapter provides an overview of the state-of-the-art of cancer theranostics from the selection of genomic, proteomic, and metabolomic biomarkers, applying molecular imaging techniques for in vivo measurement of cancer hallmarks, image-guided cancer interventions, citing examples of theranostic platforms triggered by light, magnetism, and sound to the design of nanoparticle platforms for codelivery of imaging labels and therapeutic drugs. The challenges of clinical translation of cancer theranostic approaches are also discussed.

Keywords

Biomarker; Molecular imaging; Early detection; Imaging guided cancer therapy; Nanomedicine; Personalized medicine

Outline

Cancer Theranostics: A Definition 3

Theranostic Cancer Biomarkers 4

Molecular Imaging in Cancer Theranostics 4

Imaging-Guided Cancer Therapy 5

Theranostic Platforms 5

Challenges and Future Perspectives 7

References 7

Cancer Theranostics: A Definition

Theranostics is a portmanteau of therapeutics and diagnostics. It can be diagnosis followed by therapy to stratify patients who will likely respond to a given treatment. It can also be therapy followed by diagnosis to monitor early response to treatment and predict treatment efficacy. It is also possible that diagnostics and therapeutics are codeveloped. For example, nanoplatforms can be designed to codeliver imaging and therapy components; antibodies can be labeled for imaging and conjugated with payload as antibody-drug conjugate (ADC) for therapy. Cancer theranostics, as the name implies, represents a combinatorial diagnosis and therapeutic approach to cancer disease and aims to reduce delays in treatment and ease patient care, and appears to be essential for personalized cancer treatment.

Note that in some cases theranostics is also spelled as theragnostics. A keyword search of PubMed on January 7, 2011, right before the launch of new SCI journal Theranostics, only found 95 items for “theranostic,” 63 items for “theranostics,” 29 items for “theragnostic,” and 21 items for “theragnostics.” In the past two years, literature related to theranostics grew exponentially. As of October 18, 2013, a PubMed search found 587 items for “theranostic,” 562 items for “theranostics,” 85 items for “theragnostic,” and 48 items for “theragnostics.”

There are pieces of information related to theranostics in the literature. A dedicated journal named Theranostics (www.thno.org/) was launched to open up a forum to exchange clinical and scientific information for the diagnostic and therapeutic molecular and nanomedicine community and allied professions involved in the efforts of integrating molecular imaging and molecular therapy [1]. As an evolving multidisciplinary field catering to the unmet needs of the medical world, cancer theranostics include but are not limited to the following:

• Identification of novel biomarkers to advance molecular diagnostics of cancer

• New molecular imaging probes and techniques for early detection of cancer

• Molecular imaging guided cancer therapy

• Nanoplatforms incorporating both cancer imaging and therapeutic components

Theranostic Cancer Biomarkers

Sequencing the human genome has the potential to transform the treatment of disease and the practice of medicine. One of the most profound changes to medicine is the movement toward predictive, preventive, personalized, and participatory (P4) medicine [2]. As defined by the President’s Council of Advisors on Science and Technology (PCAST), personalized medicine is the tailoring of medical treatments to the individual characteristics of each patient, and the ability to classify individuals into subpopulations based on their susceptibility to a particular disease or their responses to a specific treatment [3]. Personalized medicine therefore has the potential to optimize targeted delivery and dosing of treatments so patients can receive the most benefit with the least amount of risk, cutting out the difficulties of the current trial-and-error process many patients endure to find the correct drug and dose to treat a condition.

Human genome, epigenome, transcriptome, proteome, and metabolome analysis, high-throughput phenotypic assays, and powerful computational methods allow for delineating relevant biological networks underlying the cellular and molecular origins of cancer [4]. Efforts have been spent to develop simple, noninvasive tests that indicate disease risk, regression, and recurrence, and allow early detection to monitor disease progression and to classify patients so that they can receive the most appropriate therapy at the right time.

Early detection and definitive treatment of cancer have been shown to decrease death and suffering in epidemiologic and intervention studies. Application of genomic approaches in many malignancies has produced thousands of candidate biomarkers for detection and prognostication, yet very few have become established in clinical practice. Fundamental issues related to tumor heterogeneity, cancer progression, natural history, and biomarker performance have provided challenges to biomarker development [5]. Technical issues in biomarker assay detection limits, specificity, clinical deployment, and regulation have also slowed progress. The recent emergence of biomarkers and molecular imaging strategies for treatment selection and monitoring demonstrates the promise of cancer biomarkers. Organized efforts by interdisciplinary teams will spur progress in cancer diagnostics.

Similar to the Human Genome Project, the Human Proteome Project aims to map the entire human protein set, with respect to protein abundance, distribution, and subcellular localization, as well as protein interactions with other biomolecules and protein functions at specific time points [6]. Specific post-translational modifications (e.g., phosphorylation) and/or the status (e.g., nuclear localization) of particular proteins in cancer cells may be meaningful as potential cancer biomarkers for early detection of cancer and personalized therapeutic strategies in clinical settings.

Metabolomics can be broadly defined as the study of all metabolites produced in the body [7]. Cancer metabolome refers to low molecular weight metabolites (MW <1500 Da), including peptides, oligonucleotides, sugars, nucleosides, organic acids, ketones, aldehydes, amines, amino acids, lipids, steroids, and in some cases drugs or xenobiotics, that are germane to cancer and their changes relative to normal tissue. In general, metabolic requirements of cancer cells are quite different from those of most normal differentiated cells. Tumor cells often have a high proliferation rate, thus needing additional nutrients, and ultimately directing the nutrients into the synthesis of new biomass. With the use of metabolomics, various metabolic pathways between cancer and noncancerous tissue can be differentiated. Metabolomics is often combined with other omics disciplines for the confirmation of data from one omics by another. Currently, most of the targeted cancer therapies are based on genetic, or in some cases proteomic, analyses of human tumors. The same strategy can be applied to metabolomic analysis, evaluating the response of an individual patient to a given drug on the basis of the patient’s metabolomic status.

Molecular Imaging in Cancer Theranostics

Although in vitro diagnostic tests (genomic, transcriptomic, proteomic, and metabolomic) can identify patients who will likely respond to a particular therapy, or fail to respond to a given drug or treatment regimen, in vivo molecular imaging is a technique that uses sophisticated diagnostic imaging equipment and systems to visualize, characterize, and measure biological processes at the molecular and cellular levels in humans and other living systems [8]. In the clinic, molecular imaging enables physicians to peer into the living body to identify diseases, monitor their progression, or treat medical conditions at a molecular level. It is quite different from in vitro diagnostics, which typically require laboratory analysis of a sample, such as blood or a biopsy, as molecular imaging can study biological processes in their own physiological environment instead of by in vitro or ex vivo biopsy/cell culture labora...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Preface
• Acknowledgments
• About the Editors
• List of Contributors
• Part I: In Vitro Diagnostics
• Part II: Molecular Imaging
• Part III: Imaging-Guided Therapy
• Part IV: Theranostic Platforms
• Part V: Other
• Index