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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.
The book addresses controversies related to the origins of cancer and provides solutions to cancer management and prevention. It expands upon Otto Warburg's well-known theory that all cancer is a disease of energy metabolism. However, Warburg did not link his theory to the "hallmarks of cancer" and thus his theory was discredited. This book aims to provide evidence, through case studies, that cancer is primarily a metabolic disease requring metabolic solutions for its management and prevention. Support for this position is derived from critical assessment of current cancer theories. Brain cancer case studies are presented as a proof of principle for metabolic solutions to disease management, but similarities are drawn to other types of cancer, including breast and colon, due to the same cellular mutations that they demonstrate.
The four sections of this book cover cell and molecular biology of tumor metabolism, metabolites, tumor microenvironment, diagnostics and epigenetics. Written by international experts, it provides a thorough insight into and understanding of tumor cell metabolism and its role in tumor biology. The book is intended for scientists in cancer cell and molecular biology, scientists in drug and diagnostic development, as well as for clinicians and oncologists.
This Special Issue of Cells on “Insulin-Like Growth Factors in Development, Cancers and Aging” provides a collection of modern articles dealing with the role of insulin-like growth factors (IGF1) in cancer biology, aging and development. Featured articles explore basic and clinical aspects of the IGF1 system, including post-genomic analyses as well as novel approaches to target the IGF1 receptor (IGF1R) in oncology.
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.
New Strategies Targeting Cancer Metabolism: Anticancer Drugs, Synthetic Analogues and Antitumor Agents presents up-to-date synthetic strategies for three categories of antimetabolites: antifolates, purines and pyrimidines, the main classes of antimetabolites which are integrated into various pharmaceutical agents. Many of these antimetabolites are considered potent chemotherapeutic agents which have great potential impact on medical research. These main classes of antimetabolites are used in the treatment of critical diseases including cancer, malignancies, autoimmune diseases, and many other non-malignant diseases. Antineoplastic drugs such as alkylating agents which have significant effects are described. Novel synthetic strategies for many anticancer alkylating agents including nitrogen mustards, chlorambucil, melphalan, ifosamide, oxaliplatin and temozolomide are explored. Natural products have offered some of the most significant drugs for treating cancer, as many drugs currently in clinical use are derived from natural products as camptothecins, vinca alkaloids, and derivatives of podophyllotoxin. They provide a contribution that is essential for modern drug discovery and development. In this book, insights into a broad array of novel compounds are reviewed, well-recognized synthetic approaches are emphasized for further anticancer drug development and discovery, and the biological evaluation of novel synthesized compounds are included. This comprehensive reference is a valuable resource for medical chemists working in drug discovery and development, as well as pharmacologists and biochemists working in related fields. Provides the only resource dedicated to synthetic strategies of antimetabolites Features synthetic strategies for nucleosides and their analogues Includes coverage of purine-, pyrimidine- and antifolate-based anticancer drugs The most significant anticancer alkylating agents and natural products are demonstrated
This is the original text of Nobel Prize Laureate Dr. Otto Warburg's classic, "The Metabolism of Tumours." In this book Dr. Warburg, MD, PhD, and distinguished scientists demonstrate, through empirical evidence that: “Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one prime cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by fermentation of sugar.” All the experiments, in their original text, are included in this book.
Development of an effective anticancer therapeutic necessitates the selection of cancer-related or cancer-specific pathways or molecules that are sensitive to intervention. Several such critical yet sensitive molecular targets have been recognized, and their specific antagonists or inhibitors validated as potential therapeutics in preclinical models. Yet, majority of anticancer principles or therapeutics show limited success in the clinical translation. Thus, the need for the development of an effective therapeutic strategy persists.
“Altered energy metabolism” in cancer is one of the earliest known biochemical phenotypes which dates back to the early 20th century. The German scientist, Otto Warburg and his team (Warburg, Wind, Negelein 1926; Warburg, Wind, Negelein 1927) provided the first evidence that the glucose metabolism of cancer cells diverge from normal cells. This phenomenal discovery on deregulated glucose metabolism or cellular bioenergetics is frequently witnessed in majority of solid malignancies. Currently, the altered glucose metabolism is used in the clinical diagnosis of cancer through positron emission tomography (PET) imaging. Thus, the “deregulated bioenergetics” is a clinically relevant metabolic signature of cancer cells, hence recognized as one of the hallmarks of cancer (Hanahan and Weinberg 2011). Accumulating data unequivocally demonstrate that, besides cellular bioenergetics, cancer metabolism facilitates several cancer-related processes including metastasis, therapeutic resistance and so on. Recent reports also demonstrate the oncogenic regulation of glucose metabolism (e.g. glycolysis) indicating a functional link between neoplastic growth and cancer metabolism. Thus, cancer metabolism, which is already exploited in cancer diagnosis, remains an attractive target for therapeutic intervention as well. The Frontiers in Oncology Research Topic “Cancer Metabolism: Molecular Targeting and Implications for Therapy” emphases on recent advances in our understanding of metabolic reprogramming in cancer, and the recognition of key molecules for therapeutic targeting. Besides, the topic also deliberates the implications of metabolic targeting beyond the energy metabolism of cancer. The research topic integrates a series of reviews, mini-reviews and original research articles to share current perspectives on cancer metabolism, and to stimulate an open forum to discuss potential challenges and future directions of research necessary to develop effective anticancer strategies. Acknowledgment I sincerely thank the Frontiers for providing the opportunity and constant support throughout the process of this research topic and eBook production. I gratefully acknowledge all the authors for their valuable contributions. Finally, I would like to thank my brother, Saravana Kumar, G.K., whose personal sacrifices and unflinching encouragement made my career in science possible. References: Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: The next generation. Cell. 144(5):646-74. Warburg O, Wind F, Negelein E. 1926. Über den stoffwechsel der tumoren in körper. Klinische Wochenschrift. 5:829-32. Warburg O, Wind F, Negelein E. 1927. The metabolism of tumors in the body. J Gen Physiol. 8(6):519-30.
A must-have reference, this new edition provides practical information on treatment guidelines, details of diagnosis and therapy, and personal recommendations on patient management from experts in the field. Consistently formatted chapters allow for a user-friendly presentation for quick access of key information by the practicing clinician. Completely updated, this new edition includes all of the latest developments in treatment strategies of medical, surgical and radiation oncologists.
Molecular Targeted Radiosensitizers: Opportunities and Challenges provides the reader with a comprehensive review of key pre-clinical research components required to identify effective radiosensitizing drugs. The book features discussions on the mechanisms and markers of clinical radioresistance, pre-clinical screening of targeted radiosensitizers, 3D radiation biology for studying radiosensitizers, in vivo determinations of local tumor control, genetically engineered mouse models for studying radiosensitizers, targeting the DNA damage response for radiosensitization, targeting tumor metabolism to overcome radioresistance, radiosensitizers in the era of immuno-oncology, and more. Additionally, the book features discussions on high-throughput drug screening, predictive biomarkers, pre-clinical tumor models, and the influence of the tumor microenvironment and the immune system, with a specific focus on the challenges radiation oncologists and medical oncologists currently face in testing radiosensitizers in human cancers. Edited by two acclaimed experts in radiation biology and radiosensitizers, with thirteen chapters contributed by experts, this new volume presents an in-depth look at current developments within a rapidly moving field, with a look at where the field will be heading and providing comprehensive insight into the framework of targeted radiosensitzer development. Essential reading for investigators in cancer research and radiation biology.