Metabolism In Cancer

This open access volume will introduce recent discoveries in cancer metabolism since the publication of the first edition in 2018, providing readers with an up-to-date understanding of developments in the field. 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, the authors 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 for cancer treatment. 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 treatment. This book has four major parts. Part one will cover the basic metabolism of cancer cells, followed by a discussion of the heterogeneity of cancer metabolism in part two. Part three addresses the relationship between cancer cells and cancer-associated fibroblasts, and the new part four will explore the metabolic interplay between cancer and other diseases. This new section makes the book unique from other texts currently available on the market. The second edition will be useful for cancer metabolism researchers, cancer biologists, epidemiologists, physicians, health care professionals in related disciplines, policymakers, marketing and economic strategists, among others. It may also be used in courses such as intro to cancer metabolism, cancer biology, and related biochemistry courses for undergraduate and graduate students.

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.

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.

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.

The Optimal Terrain Ten Protocol to Reboot Cellular Health Since the beginning of the twentieth century, cancer rates have increased exponentially--now affecting almost 50 percent of the American population. Conventional treatment continues to rely on chemotherapy, surgery, and radiation to attack cancer cells. Yet research has repeatedly shown that 95 percent of cancer cases are directly linked to diet and lifestyle. The Metabolic Approach to Cancer is the book we have been waiting for--it offers an innovative, metabolic-focused nutrition protocol that actually works. Naturopathic, integrative oncologist and cancer survivor Dr. Nasha Winters and nutrition therapist Jess Higgins Kelley have identified the ten key elements of a person's "terrain" (think of it as a topographical map of our body) that are crucial to preventing and managing cancer. Each of the terrain ten elements--including epigenetics, the microbiome, the immune system, toxin exposures, and blood sugar balance--is illuminated as it relates to the cancer process, then given a heavily researched and tested, non-toxic and metabolic, focused nutrition prescription. The metabolic theory of cancer--that cancer is fueled by high carbohydrate diets, not "bad" genetics--was introduced by Nobel Prize-laureate and scientist Otto Warburg in 1931. It has been largely disregarded by conventional oncology ever since. But this theory is resurging as a result of research showing incredible clinical outcomes when cancer cells are deprived of their primary fuel source (glucose). The ketogenic diet--which relies on the body's production of ketones as fuel--is the centerpiece of The Metabolic Approach to Cancer. Further, Winters and Kelley explain how to harness the anticancer potential of phytonutrients abundant in low-glycemic plant and animal foods to address the 10 hallmarks of cancer--an approach Western medicine does with drug based therapies. Their optimized, genetically-tuned diet shuns grains, legumes, sugar, genetically modified foods, pesticides, and synthetic ingredients while emphasizing whole, wild, local, organic, fermented, heirloom, and low-glycemic foods and herbs. Other components of their approach include harm-reductive herbal therapies like mistletoe (considered the original immunotherapy and common in European cancer care centers) and cannabinoids (which shrink tumors and increase quality of life, yet are illegal in more than half of the United States). Through addressing the ten root causes of cancer and approaching the disease from a nutrition-focused standpoint, we can slow cancer's endemic spread and live optimized lives.

Starving Cancer Cells: Evidence-Based Strategies to Slow Cancer Progression — A Selection of Readings for Health Services Providers presents an edited and annotated collection of recent medical journal publications and abstracts illustrating new approaches to treatment derived from the metabolic theory of cancer. It intends to shed an early light on a relatively new approach to our understanding of the cancer cell idiosyncratic metabolic dysfunction, and on evidence-based new treatment strategies derived from that understanding. The book discusses topics such as tumor starvation by L-arginine deprivation; L-canavanine depriving tumors of L-arginine in pancreatic, multiple myeloma and breast cancer; glucose deprivation and intermittent fasting; glutamine uptake in cancer; the relation of oxygen-starved cancer cells with aspartate; and reducing tolerance of tumor cells to nutrition starvation. The content is presented in a contextualized and practical way in order to facilitate the transition from bench to bedside. This is a valuable resource for practitioners, oncologists and other members of healthcare chain who are interested in learning more about the most recent tumor cell starvation strategies and how they can improve overall treatment outcome. Provides extensive comments on scientific publications detailing recent findings about tumor cell auxotrophy applied to tumor cell starvation strategies Helps the reader to find relevant and practical information on cancer cell starvation, otherwise spread through niched specialized journals, in one single place Comments on the recent findings putting them in context of clinical practice in order to provide the reader with means of translating high level research to the clinics

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.

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.