Download or read book New Strategies Targeting Cancer Metabolism written by Galal H. Elgemeie and published by Elsevier. This book was released on 2022-05-17 with total page 630 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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

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 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 Molecular Targeted Radiosensitizers written by Henning Willers and published by Springer Nature. This book was released on 2020-08-10 with total page 370 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

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 Cancer Cell Metabolism A Potential Target for Cancer Therapy written by Dhruv Kumar and published by Springer Nature. This book was released on 2020-02-13 with total page 191 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

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 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 Targeting Cancer Cell Metabolism as a Therapeutic Strategy written by Barbara Julieta Chaneton and published by . This book was released on 2014 with total page 120 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Carbohydrate based Inducers of Cellular Stress for Targeting Cancer Cell Metabolism written by Fidelis Toloyi Ndombera and published by . This book was released on 2018 with total page 200 pages. Available in PDF, EPUB and Kindle. Book excerpt: ABSTRACT CARBOHYDRATE-BASED INDUCERS OF CELLULAR STRESS FOR TARGETING CANCER CELL METABOLISM by FIDELIS TOLOYI NDOMBERA May 2018 Advisor: Dr. Young-Hoon Ahn Major: Chemistry (Biochemistry) Degree: Doctor of Philosophy Metabolic reprogramming and redox control of cancer cells is vital for their proliferation, but also provides selective strategies for treating cancer. Increased generation of reactive oxygen species (ROS) and an intricate control of redox status in cancer cells relative to normal cells provide a basis for designing ROS-inducing anticancer agents. In my work, I designed, synthesized and evaluated carbohydrate-based small molecules for ROS-generation, cytotoxicity and redox signaling and stress response. Our data from assays, including cell viability assays, enzyme inhibition studies, Western blot studies, click chemistry, and metabolomics, reveal that our compound (K8A) is more potent than 2-DG, a well-known carbohydrate-derived inhibitor of glycolysis. We reported discovery of carbohydrate-based small molecules with the property of blocking altered metabolic activity and enhancing ROS with potential therapeutic benefits for targeting cancer cells. Importantly, we investigated the mechanism of action of our potent compound that involve disruption of protein glycosylation in cancer with downstream effects on cancer metabolism.

Download or read book Cancer Cell Metabolism written by and published by . This book was released on 2020 with total page 190 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Targeting Cancer Metabolism written by Bevan Gang and published by . This book was released on 2014 with total page 268 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Warburg effect occurs in 90% of tumors, where glycolysis is favored despite the presence of oxygen. The activity of pyruvate dehydrogenase kinases (PDKs) is increased in cancer cells, suppressing glucose oxidation. Inhibition of PDKs can redirect glucose flux into the mitochondria, reversing the Warburg effect. Dichloroacetate (DCA) is a relatively non-toxic PDK inhibitor that inhibits all four isoforms of PDK with differing potency. We examined the determinants of DCA sensitivity, the ability of DCA to enhance apoptosis, and how DCA regulates cell metabolism. We found in a range of cancer types, that all four PDK isoforms can be expressed and contribute to tumor metabolism. DCA inhibited cancer cell growth in vivo and in vitro, activated PDH and reduced lactate production. The magnitude of DCA growth inhibition correlated with the PDK expression profiles of the cells, with PDK3 (highest Ki for DCA) conferring low sensitivity towards DCA. PDK2 siRNA-knockdown inhibited growth to a similar extent to DCA, whilst PDK3 knockdown significantly increased sensitivity to DCA, confirming sensitivity to DCA is determined by PDK expression. Further examination of PDKs in patient samples will increase the likelihood of DCA being successfully translated into clinical use, with the PDK expression profile being a biomarker for sensitivity to DCA. The mechanisms by which DCA can sensitize cancer cells towards apoptosis were investigated, as we observed that DCA increased hypoxia-induced apoptosis. DCA enhanced the effects of 4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid (PENAO; a novel anti-mitochondrial agent) in vitro. DCA increased ROS levels, which were fully responsible for enhancing PENAO apoptosis in MDA-MB-231 cells, but only partially in T-47D cells. The two cell lines were metabolically distinct, potentially explaining the different mechanisms by which DCA enhanced apoptosis. PDK knockdown experiments revealed that DCA could enhance apoptosis via off-target effects. The pro-apoptotic proteins Noxa and Puma were investigated, however DCA did not alter their expression. DCA however depolarized the mitochondrial membrane potential in T-47D cells, suggesting that this is an additional mechanism of DCA apoptosis enhancement in these cells. Nevertheless, DCA sensitized all cancer cell lines tested towards apoptosis. Thus DCA has potential to be used in combination with other cytotoxic agents in order to reduce their adverse effects. To understand the mechanism of action, the metabolic effects of DCA on cancer cells were investigated. Gas chromatography-mass spectrometry metabolomics revealed a general trend of increase in the proportion of anabolic metabolites upon DCA treatment. Furthermore, long-term DCA treatment resulted in DCA-resistance, which was accompanied by correlating changes in the PDK expression profile. These findings thus open avenues of further exploration on the mechanism of DCA action and resistance factors. Our findings provide potential biomarkers for sensitivity to DCA, and evidence that DCA can be combined with other therapies for enhanced anti-cancer effects. We have opened future directions of identifying DCA-resistance factors. This will allow using drugs in combination with DCA that specifically target these resistance factors. Collectively our work will allow DCA to have greater success in clinical trials by being able to target patients most likely to respond.

Download or read book Tumor Cell Metabolism written by Sybille Mazurek and published by Springer. This book was released on 2015-01-19 with total page 373 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Innovative Medicine written by Kazuwa Nakao and published by Springer. This book was released on 2015-10-13 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.

Download or read book Therapeutic Targeting of Cancer Stem Like Cells CSC The Current State of the Art written by Cyril Corbet and published by Frontiers Media SA. This book was released on 2020-04-03 with total page 192 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Strategies for the Precision Targeting of Nucleotide Metabolism in Cancer written by Evan Robert Abt and published by . This book was released on 2019 with total page 258 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer cell proliferation and survival are dependent upon on a sufficient supply of deoxyribonucleotide triphosphates (dNTPs), the substrates for DNA replication. dNTPs are produced by convergent intracellular metabolic pathways, either by the de novo pathway which utilizes glucose and amino acid precursors or by the salvage pathway which allows for the scavenging of preformed nucleosides from the environment. Despite its fundamental nature, the regulation of nucleotide biosynthesis by intracellular signaling networks in cancer cells is poorly defined and the implications of this control are unclear. Here we systematically evaluate the regulation of cancer cell nucleotide metabolism by two signaling networks, the replication stress response pathway and signaling elicited by the cytokine interferon. Armed with new insights into the regulation of nucleotide metabolism in cancer we develop new, rationally designed therapeutic strategies to be translated for the treatment of precisely defined patient populations. Chapter 1 provides an introduction to nucleotide metabolism function and regulation in cancer. Chapter 2 concerns the investigation of nucleotide metabolism regulation by the replication stress response signaling pathway. Here we define a link between the proximal replication stress response kinase ataxia telangiectasia and Rad3-related protein (ATR) and rate-limiting enzymes in de novo and salvage nucleotide biosynthetic pathways: ribonucleotide reductase (RNR) and deoxycytidine kinase (dCK). In cancer cells, ATR inhibition produces a collateral dependency on RNR and dCK activity. We demonstrate that simultaneously targeting ATR, RNR and dCK using small molecule inhibitors effectively eradicates acute lymphoblastic leukemia cells in vitro and in vivo. In Chapter 3 we report an investigation of nucleotide metabolism regulation by the pleiotropic cytokine type I interferon. We determine that interferon signaling is constitutive in pancreatic ductal adenocarcinoma (PDAC) patient tumors and xenograft models and is driven by the cGAS/STING pathway. In PDAC cells, interferon signaling triggers a decrease in dNTP pool abundance and up-regulates dNTP phosphohydrolysis mediated by sterile alpha-motif and histidine-aspartate domain-containing protein 1 (SAMHD1). Activation of ATR is a compensatory response to this stress and we find that interferon signaling triggers a dependency on ATR activity in a subset of PDAC models. Chapter 4 concerns the identification of a cancer cell metabolic vulnerability that results from impaired dNTP catabolism. Here we show that inhibition of purine nucleoside phosphorylase (PNP) selectively induces dNTP pool imbalance and cell death in cancer cells lacking the phosphohydrolase SAMHD1. In this chapter we define a new synthetic lethal interaction in cancer and demonstrate that SAMHD1 deficiency is a requisite biomarker for PNP inhibitor activity. In Chapter 5 we present the development and application of a cell-based metabolic modifier screening platform that leverages the redundancy in pyrimidine metabolism for the discovery of specific modulators of convergent nucleotide biosynthetic pathways. Here we report the identification and characterization of selective small molecule inhibitors of the pyrimidine de novo pathway enzyme dihydroorotate dehydrogenase and of nucleoside transporters which are essential for nucleoside salvage pathway activity.

Download or read book Anticancer Drugs written by Niamh M O’Boyle and published by MDPI. This book was released on 2019-10-11 with total page 214 pages. Available in PDF, EPUB and Kindle. Book excerpt: The past decades have seen major developments in the understanding of the cellular and molecular biology of cancer. Significant progress has been achieved regarding long-term survival for the patients of many cancers with the use of tamoxifen for treatment of breast cancer, treatment of chronic myeloid leukaemia with imatinib, and the success of biological drugs. The transition from cytotoxic chemotherapy to targeted cancer drug discovery and development has resulted in an increasing selection of tools available to oncologists. In this Special Issue of Pharmaceuticals, we highlight the opportunities and challenges in the discovery and design of innovative cancer therapies, novel small-molecule cancer drugs and antibody–drug conjugates, with articles covering a variety of anticancer therapies and potential relevant disease states and applications. Significant efforts are being made to develop and improve cancer treatments and to translate basic research findings into clinical use, resulting in improvements in survival rates and quality of life for cancer patients. We demonstrate the possibilities and scope for future research in these areas and also highlight the challenges faced by scientists in the area of anticancer drug development leading to improved targeted treatments and better survival rates for cancer patients.