Tumor Metabolome Targeting And Drug Development

In this volume, the major metabolic alterations identified in cancer and tumor-associated cells are explored, including discussions of former and emerging approaches to drug development in targeting cancer cell metabolism. The metabolic network in cells promotes the generation of both energy and biomass needed for them to grow, divide and differentiate. However, the metabolism of malignant cells generally varies from that of normal cells. These differences provide a platform for the discovery of new approaches to targeting potential vulnerabilities in cancer cells for therapeutic options Some of the significant changes that occur involve ATP production and consumption that modulates the ATP to ADP ratio, hypoxia and the effects of reactive oxygen species on glycolysis, regulation of mitochondrial respiration, induction and suppression of autophagy, and the Warburg effect and “reverse” Warburg effect--these topics and more are discussed in this volume.

Cancer metabolomics is a rapidly evolving field that aims for a comprehensive dissection of the metabolic phenotypes and functional network of metabolites in human cancers. State of the art metabolomics tools have been developed and applied to studying cancer metabolism and developing metabolic targets for improved diagnosis, prognosis and therapeutic treatment of human cancers. Chapters are written by subject experts in the field of cancer metabolomics with cross-disciplinary contributions. Coverage includes advanced metabolomics technologies and methodologies, including chemical isotope labelling liquid chromatography - mass spectrometry, capillary ion chromatography - mass spectrometry, 2-D gas chromatography – mass spectrometry, capillary electrophoresis – mass spectrometry, nuclear magnetic resonance spectroscopy, shotgun lipidomics, tracer-based metabolomics, microbial metabolomics, mass spectrometry imaging for single cell metabolomics and functional metabolomics. In addition, the book highlights new discoveries in cancer metabolism such as hypoxia inducible factor pathway, isocitrate dehydrogenase 1 mutation and oncometabolites. Finally, contributors focus on the translational applications of metabolomics in human cancers such as glioma, head and neck cancer, and gastric cancer. This new volume will be a unique reference source for cancer researchers and promote applications of metabolomics in understanding cancer metabolism.

Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

This book illustrates various aspects of cancer cell metabolism, including metabolic regulation in solid tumours vs. non-solid tumours, the molecular pathways involved in its metabolism, and the role of the tumour microenvironment in the regulation of cancer cell metabolism. It summarizes the complexity of cancer cell metabolism in terms of the switch from anaerobic to aerobic glycolysis and how mitochondrial damage promotes aerobic glycolysis in cancer cells. The respective chapters provide the latest information on the metabolic remodelling of cancer cells and elucidate the important role of the signalling pathways in reprogramming of cancer cell metabolism. In addition, the book highlights the role of autophagy in cancer cell metabolism, and how metabolic crosstalk between cancer cells and cancer-associated fibroblasts promotes cancer cell progression. In closing, it summarizes recent advancements in drug development through targeting cancer metabolism.

This book describes the state of the art in the application of NMR spectroscopy to metabolomics and will be a key title for researchers and practitioners.

The metabolomics approach, defined as the study of all endogenously-produced low-molecular-weight compounds, appeared as a promising strategy to define new cancer biomarkers. Information obtained from metabolomic data can help to highlight disrupted cellular pathways and, consequently, contribute to the development of new-targeted therapies and the optimization of therapeutics. Therefore, metabolomic research may be more clinically translatable than other omics approaches, since metabolites are closely related to the phenotype and the metabolome is sensitive to many factors. Metabolomics seems promising to identify key metabolic pathways characterizing features of pathological and physiological states. Thus, knowing that tumor metabolism markedly differs from the metabolism of normal cells, the use of metabolomics is ideally suited for biomarker research. Some works have already focused on the application of metabolomic approaches to different cancers, namely lung, breast and liver, using urine, exhaled breath and blood. In this Special Issue we contribute to a more complete understanding of cancer disease using metabolomics approaches.

Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution. The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis and modeling. This new standard effectively eliminates the differing methodologies used in studies and creates a unified approach. Readers will learn the advantages and disadvantages of the various techniques discussed, as well as potential difficulties inherent to all steps in the biomarker discovery process. A vital resource for biochemists, biologists, analytical chemists, bioanalytical chemists, clinical and medical technicians, researchers in pharmaceuticals, and graduate students, Proteomic and Metabolomic Approaches to Biomarker Discovery provides the information needed to reduce clinical error in the execution of research. Describes the use of biomarkers to reduce clinical errors in research Includes techniques from a range of biomarker discoveries Covers all steps involved in biomarker discovery, from study design to study execution

This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications. Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.