Tumor Cell Metabolism

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 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.

Metabolism of glucose, lipids, amino acids, and nucleotides represents the fundamental capability of host to utilize distinct nutrients and energy to support diverse function of different cell lineages. Cancer cells undergo the Warburg Effect to adapt to the microenvironment composed by stromal cells and immune cells. The crosstalk among cancer cells and immune cells orchestrate tumor progression. In the tumor microenvironment, immune cells also show metabolic reprogramming. For example, naive or memory T cells switch from the oxidation of fatty acids to glycolysis and glutaminolysis after activation; meanwhile massive glucose and glutamine are transported into cells to meet their metabolic demands. Defective glucose or glutamine metabolism impairs the differentiation and expansion of helper T cells. The molecular pathways that control immune cell metabolism and function are intimately linked. Understanding such metabolic reprogramming of immune cells in the tumor microenvironment could offer new directions in manipulation of peripheral immune responses. Recent findings in immune cell metabolism hold the promising possibilities by metabolic manipulation of immune cells towards clinical therapeutics for treating cancer. This Research Topic includes updated findings and views in the metabolism of cancer cells and immune cells in the tumor microenvironment.

The present eBook presents one review, five mini-reviews, and an opinion article on the achievements and perspectives of studies on important aspects of cancer cell metabolic reprogramming whose mechanisms and regulation are still largely elusive. It also sheds light on certain novel functional components, which rewires cell metabolism in tumor transformation.

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.

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 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.