Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer. This book was released on 2018-06-26 with total page 186 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Metabolic Heterogeneity in Breast Cancer written by Ying-Hui Ko and published by . This book was released on 2016 with total page 286 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is the second leading cause of cancer deaths in women and hence understanding the pathophysiology of this disease is necessary to develop novel treatments. Metabolic heterogeneity with transfer of catabolites between fibroblasts and breast cancer epithelial cells occurs in breast, ovarian and prostate carcinomas. Metabolic heterogeneity promotes tumor growth and resistance to anticancer agents. Fibroblasts have high rates of autophagy, catabolism, glycolysis and excrete large amounts of lactate and glutamine. Conversely, cancer epithelial cells use lactate and glutamine at high rates as substrates of oxidative phosphorylation (OXPHOS) mitochondrial metabolism and are more resistant to autophagy. Glutamine is a crucial amino acid in cancer cell metabolism and is the most abundant amino acid in plasma. Glutamine is catabolized to alpha-ketoglutarate through glutaminolysis and enters the tricarboxylic acid (TCA) cycle and increases OXPHOS in proliferating cells. Glutaminolysis via glutamate leads to the generation of the antioxidant glutathione, which protects cells from oxidative stress induced apoptosis. Ammonia is also a by-product of glutamine catabolism, which is a diffusible inducer of autophagy. TIGAR is a 2,6 phospho-fructose bisphosphatase which reduces glycolysis and apoptosis in cells. TIGAR is highly expressed in the majority of human breast carcinoma cells. Breast cancer cells tend to have low glycolytic rates and high lactate and glutamine uptake and catabolism rates. The mechanisms by which stromal-epithelial metabolic heterogeneity promotes tumor growth are unknown and we don't know the effects of modulators of glycolysis and catabolites such as glutamine and lactate on cancer growth. It is unknown if TIGAR modulates lactate and glutamine catabolism and mitochondrial OXPHOS. I hypothesized that TIGAR and catabolites such as glutamine and lactate might drive tight metabolic heterogeneity in breast cancer. I have discovered using cellular and animal models that glutamine increases mitochondrial biogenesis, decreases autophagy and protects breast cancer cells from apoptosis. Glutamine also induces a catabolic phenotype in cancer-associated fibroblasts (CAFs). TIGAR overexpression in carcinoma cells induces metabolic heterogeneity between breast carcinoma cells and CAFs. TIGAR in carcinoma cells induces lactate and glutamine catabolism markers and higher NADPH levels and reduces glycolysis in carcinoma cells while as TIGAR induces a glycolytic phenotype in fibroblasts when oveerexpressed in carcinoma cells. Finally, TIGAR overexpression in carcinoma cells increases tumor size and weight in orthotopic xenograft models of breast cancer.
Download or read book Tumor Organoids written by Shay Soker and published by Humana Press. This book was released on 2017-10-20 with total page 225 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book The Heterogeneity of Cancer Metabolism written by Anne Le and published by Springer Nature. This book was released on 2021-05-20 with total page 283 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Cancer as a Metabolic Disease written by Thomas Seyfried and published by John Wiley & Sons. This book was released on 2012-05-18 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Epithelial Mesenchymal Plasticity in Cancer Metastasis written by Mohit Kumar Jolly and published by MDPI. This book was released on 2020-12-29 with total page 512 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent studies have highlighted that epithelial-mesenchymal transition (EMT) is not only about cell migration and invasion, but it can also govern many other important elements such as immunosuppression, metabolic reprogramming, senescence-associated secretory phenotype (SASP), stem cell properties, therapy resistance, and tumor microenvironment interactions. With the on-going debate about the requirement of EMT for cancer metastasis, an emerging focus on intermediate states of EMT and its reverse process mesenchymal-epithelial transition (MET) offer new ideas for metastatic requirements and the dynamics of EMT/MET during the entire metastatic cascade. Therefore, we would like to initiate discussions on viewing EMT and its downstream signaling networks as a fulcrum of cellular plasticity, and a facilitator of the adaptive responses of cancer cells to distant organ microenvironments and various therapeutic assaults. We hereby invite scientists who have prominently contributed to this field, and whose valuable insights have led to the appreciation of epithelial-mesenchymal plasticity as a more comprehensive mediator of the adaptive response of cancer cells, with huge implications in metastasis, drug resistance, tumor relapse, and patient survival.
Download or read book Targeting Metabolic Vulnerabilities in Breast Cancer Subtypes written by Martin Peter Ogrodzinski and published by . This book was released on 2020 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is a highly prevalent and deadly disease. Globally, it is the most diagnosed cancer in women and is responsible for the most cancer-related deaths among women. Breast cancer is also a remarkably heterogeneous disease, with clear variability in clinical parameters including histological presentation, receptor status, and gene expression patterns that differ between patients. A significant amount of effort has been spent characterizing breast cancer into subtypes, with the main goal of improving patient outcomes by: 1) designing targeted therapies, and 2) improving our ability to determine patient prognosis. While scientists have made significant strides in meeting these goals, we still lack targeted therapies for some subtypes of breast cancer, and current therapies often fail to provide a lasting cure. Thus, additional research is needed to improve patient care. One promising area in breast cancer research is cancer metabolism. Using metabolism as a therapeutic target is rapidly gaining traction, as it is now widely appreciated that cancer cells exhibit significant differences in metabolism compared to normal cells. The primary goal of this dissertation is to study the metabolism of distinct subtypes of breast cancer and identify metabolic vulnerabilities that can be used to effectively treat each subtype.This thesis will begin with a review of current classification strategies for breast cancer subtypes and knowledge regarding subtype-specific metabolism. It will also consider modern techniques for targeting breast cancer metabolism for therapeutic benefit. Breast cancer heterogeneity and metabolism are investigated using cell lines and tumors derived from the MMTV-Myc mouse model, which mimics the complexity observed in human disease. Cell lines derived from two histologically defined subtypes, epithelial-mesenchymal transition (EMT) and papillary, are used to establish clear metabolic profiles for each subtype. Metabolic vulnerabilities are identified in glutathione biosynthesis and the tricarboxylic acid cycle in the EMT subtype and nucleotide biosynthesis is determined to be a metabolic weakness in the papillary subtype. It is further shown that pharmacologically targeting each of these metabolic pathways has the greatest effect on reducing proliferation when used against the vulnerable subtype. These in vitro findings are then expanded upon by integrating genomic and metabolomic data acquired from in vivo tumors. In vivo experiments reveal that the EMT and papillary tumors prefer parallel pathways to generate nucleotides, with the EMT subtype preferring to salvage nucleotides while the papillary subtype prefers to produce nucleotides de novo. CRISPR/Cas9 gene editing is used to functionally characterize the metabolic effects of targeting nucleotide salvage and de novo biosynthesis in the EMT and papillary subtypes, and determine that targeting the preferred pathway of each subtype is most effective at slowing tumor growth.Overall, this work demonstrates the power of using metabolism as a therapeutic target of breast cancer, and further shows that metabolic vulnerabilities specific to individual subtypes can be used effectively to guide personalized medicine.
Download or read book NMR based Metabolomics written by Hector C Keun and published by Royal Society of Chemistry. This book was released on 2018-01-17 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Metabolism in Cancer written by Thorsten Cramer and published by Springer. This book was released on 2016-08-24 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Epigenetic and Metabolic Regulators of Breast Carcinogenesis written by Iman Mamdouh Talaat and published by Frontiers Media SA. This book was released on 2024-07-23 with total page 168 pages. Available in PDF, EPUB and Kindle. Book excerpt: Breast cancer is the most common tumor in females worldwide. Cancer epigenetics and metabolic reprogramming are known cancer hallmarks. Recent advances in the field of epigenetics include histone modification, DNA methylation, and non-coding RNAs. In contrast to genetic modifications, epigenetics refers to a set of dynamic alterations. By controlling the on and off states of oncogenes and tumor suppressor genes, as well as re-engineering the tumor microenvironment, epigenetics plays a crucial role in the initiation and progression of carcinogenesis. Additionally, the complex process of metabolic reprogramming is required for both malignant transformation and tumor development, including invasion and metastasis. Furthermore, reprogrammed metabolic activities have been utilized to diagnose, monitor, and treat cancer patients. In tumor tissues, metabolic heterogeneity was found to take a role in the adaptation to the microenvironment drastic changes resulting from current therapeutic modalities.
Download or read book Lineage restricted Metabolic Identities of Mammary Epithelial Cells written by Mathepan Mahendralingam and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer metabolism has been proposed to adapt the metabolic network from its tissue-of-origin. However, breast cancer is not a disease of a singular origin. There are multiple epithelial subpopulations that serve as the culprit cell-of-origin, giving rise to distinct breast cancer subtypes. Knowledge surrounding the metabolic identities of normal mammary epithelial cells (MEC) is limited. Proteomic profiling of primary FACS-purified human MECs revealed that each subpopulation possesses distinct metabolic networks. Luminal progenitors were enriched for electron transport chain subunits, had an enhanced capacity to undergo oxidative phosphorylation and were vulnerable to Complex I inhibition. Basal cells were more glycolytic, but their progenitor capacity was still dependent on mitochondrial activity. Targeting these pathways with inhibitors exposed lineage-restricted metabolic vulnerabilities. Furthermore, breast cancer subtypes demonstrated significant activity for the metabolic cluster of their cell-of-origin. My work demonstrates that normal MEC have lineage-restricted metabolic identities, which can partly explain the metabolic heterogeneity observed in breast cancer.
Download or read book Metabolic Abnormalities and Breast Cancer Challenges From Bench to Bedside written by Xiaosong Chen and published by Frontiers Media SA. This book was released on 2022-08-01 with total page 211 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Cancer Metabolism Molecular Targeting and Implications for Therapy written by Shanmugasundaram Ganapathy-Kanniappan and published by Frontiers Media SA. This book was released on 2017-11-03 with total page 116 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book The Tumour Microenvironment written by Jamie A. Goode and published by John Wiley & Sons. This book was released on 2001-11-28 with total page 322 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ergebnisse von in vitro-Studien lassen vermuten, dass sich der pH-Wert in einem Tumor auf die Wirksamkeit von Chemo- oder Strahlentherapien auswirken kann. Wie aber sieht die Beziehung zwischen der Tumorentwicklung und dem pH-Wert aus? Können ein niedriger pH-Wert oder ein Sauerstoffmangel die Carcinogenese hemmen? Wo bieten sich therapeutische Ansätze? Anwort auf diese und andere Fragen finden Sie in diesem Band. In interdisziplinärer Weise wurden Beiträge aus der Grundlagenforschung und der klinischen Praxis zusammengetragen.
Download or read book The Molecular Basis of Human Cancer written by William B. Coleman and published by Humana Press. This book was released on 2016-11-11 with total page 868 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers the concepts of molecular medicine and personalized medicine. Subsequent chapters cover the topics of genomics, transcriptomics, epigenomics, and proteomics, as the tools of molecular pathology and foundations of molecular medicine. These chapters are followed by a series of chapters that provide overviews of molecular medicine as applied broadly to neoplastic, genetic, and infectious diseases, as well as a chapter on molecular diagnostics. The volume concludes with a chapter that delves into the promise of molecular medicine in the personalized treatment of patients with complex diseases, along with a discussion of the challenges and obstacles to personalized patient care. The Molecular Basis of Human Cancer, Second Edition, is a valuable resource for oncologists, researchers, and all medical professionals who work with cancer.
Download or read book The Association of Tissue Architecture Changes Metabolic Heterogeneity in Epithelial Cancer Cells written by Maia Al-Masri and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: "Epithelial cells interact to form architecturally organized structures in tissues, with strict control of motility, proliferation and metabolic signaling, each of which is altered during cancer progression. Loss of epithelial organization and tissue architecture is associated with the acquisition of a malignant phenotype during breast cancer initiation and throughout its progression. The changes in tissue architecture that accompany the development of breast cancer is an excellent model, that develops through architecturally different preinvasive stages that include benign lesions such as ductal carcinoma in situ (DCIS), which are risk factors for the development of invasive disease (IDC). Currently, DCIS accounts for 20% of breast cancer diagnoses, and about half are expected to progress to IDC. No clear biomarkers and histological features exist to distinguish DCIS that will or will not progress to invasive disease. Metabolic plasticity enables cancer cells to switch between glycolysis and oxidative phosphorylation to adapt to changing conditions during cancer progression, whereas metabolic dependencies limit plasticity. However, understanding how metabolic programs change during cancer progression and the influence of the architectural and mechanical environments on metabolic dependency and plasticity remained to be fully established. Accordingly, to understand a role for the architectural environment in these processes we examined metabolic heterogeneity and dependencies of cancer cells using both in vitro models, cultured in flat (two-dimensional; 2D) and organotypic (three-dimensional; 3D) environments, and an in vivo model. The hypothesis of my thesis is that tissue architecture influences metabolic programs/phenotypes in epithelial cancer cells. I first examined the impact of epithelial architecture on metabolic plasticity using 2D and 3D cultures with diverse epithelial cancer cells. The propagation of cells in flat cultures is technically simple and enables maintenance of long-term exponential growth. However, they lack architectural information that regulates many epithelial cell behaviors, which are thought to be more accurately recapitulated in organotypic cultures whereby cells can more freely associate with the microenvironment on all sides. In contrast, cells in organotypic cultures preserve mechanical cell-ECM interactions and organize into tissue-relevant architectures that regulate signaling and growth. Recent studies have noted metabolic differences between 2D and 3D cultures. In this thesis I show that cancer cells in flat 2D cultures exist in a high energy state (oxidative phosphorylation), are glycolytic, and depend on glucose and glutamine for growth. In contrast, cells in organotypic culture exhibit lower energy and glycolysis, with extensive metabolic plasticity to maintain growth during glucose or amino acid deprivation. Furthermore, our metabolomic and gene-expression data indicate that the architectural environment strongly influences signaling and metabolic pathways related to amino acid metabolism. Expression of KRASG12V in organotypic cells drives glucose dependence, however cells retain metabolic plasticity to glutamine deprivation. Finally, these data reveal that mechanical properties control metabolic plasticity"--
Download or read book Keto for Cancer written by Miriam Kalamian and published by Chelsea Green Publishing. This book was released on 2017 with total page 402 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
