The Heterogeneity Of Cancer Metabolism

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.

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.

Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.

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.

Improved understanding of the cellular and molecular makeup of tumors in the last 30 years has unraveled a previously unexpected level of heterogeneity among tumor cells as well as within the tumor microenvironment. The concept of tumor heterogeneity underlines the realization that different tumors can display significant differences in their genomic content as well as in their overall behavior. Our capacity to better understand the heterogeneous make up of tumors has very important consequences on our ability to design efficient therapeutic strategies to improve patient survival. This book highlights several aspects of tumor heterogeneity in the context of metastatic development and summarize some of the challenges posed by heterogeneity for tumor diagnostics and therapeutic management of tumors.

This book offers significant coverage on different aspects of cancer from risk factors to the mechanisms leading to tumor progression and metastasis. Although tremendous progress has been made in cancer research and treatment, cancer metastasis remains a major unmet clinical need. The life and death of many cancer patients hangs on the degree of metastasis. This book provides new perspectives for diagnosis and cancer therapy. It includes new technologies and a new basis for current cancer therapies. To guarantee the high quality of this book, important topics are included and rigorously discussed in a simple and authentic way. The book addresses important challenges governing tumor progression and metastasis and brings new responses to both diagnosis and therapy. This book is a great source of knowledge and will be useful for researchers, medical doctors, oncologists, graduate and medical students, continued medical educators, health care providers, and all individuals interested in understanding cancer and its challenges.

A Comprehensive Guide for Patients and Practitioners Although evidence supporting the benefits of ketogenic diet therapies continues to mount, there is little to guide those who wish to adopt this diet as a metabolic therapy for cancer. Keto for Cancer fills this need. Inspired by the work of Dr. Thomas N. Seyfried, PhD, nutritionist Miriam Kalamian has written the first book to lay out comprehensive guidelines that specifically address the many challenges associated with cancer, and particularly the deep nutritional overhaul involved with the ketogenic diet. Kalamian, a leading voice in the keto movement, is driven by passion from her own experience in using the ketogenic diet for her young son. Her book addresses the nuts and bolts of adopting the diet, from deciding whether keto is the right choice to developing a personal plan for smoothly navigating the keto lifestyle. It is invaluable for both beginners and seasoned users of the ketogenic diet, as well as for health-care professionals who need a toolkit to implement this targeted metabolic therapy. The book guides readers to a deeper understanding of the therapeutic potential of the ketogenic diet--which extends well beyond simply starving cancer--emphasizing the powerful impact the diet has on the metabolism of cancer cells. Nutritional nuances are explored in sections such as "Fasting Protocols" and "Know What's in the Foods You Eat" while meal templates and tracking tools are provided in "Preparing Keto Meals." Kalamian also discusses important issues such as self-advocacy. Readers of Keto for Cancer are empowered to "get off the bench and get in the game." To that end, Kalamian offers tips on how to critically examine cancer-care options then incorporate what resonates into a truly personalized treatment plan.