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 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 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 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 CRISPR Cas Enzymes written by and published by Academic Press. This book was released on 2019-01-25 with total page 451 pages. Available in PDF, EPUB and Kindle. Book excerpt: CRISPR-Cas Enzymes, Volume 616, the latest release in the Methods in Enzymology series, continues the legacy of this premier serial with quality chapters authored by leaders in the field. Topics covered in this release include CRISPR bioinformatics, A method for one-step assembly of Class 2 CRISPR arrays, Biochemical reconstitution and structural analysis of ribonucleoprotein complexes in Type I-E CRISPR-Cas systems, Mechanistic dissection of the CRISPR interference pathway in Type I-E CRISPR-Cas system, Site-specific fluorescent labeling of individual proteins within CRISPR complexes, Fluorescence-based methods for measuring target interference by CRISPR-Cas systems, Native State Structural Characterization of CRISRP Associated Complexes using Mass Spectrometry, and more. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Enzymology series Updated release includes the latest information on the CRISPR-Cas Enzymes
Download or read book Personalized Medicine in Oncology written by Ari VanderWalde and published by . This book was released on 2022 with total page 174 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nowhere is the explosion in comprehensive genomic testing more evident than in oncology. Multiple consensus guidelines now recommend molecular testing as the standard of care for most metastatic tumors. To aid in the advancement of this rapidly changing field, we intend this Special Issue of JPM to focus on technical developments in the genomic profiling of cancer, detail promising somatic alterations that either are, or have a high likelihood of being, relevant in the near future, and to address issues related to the pricing and value of these tests.The last few years have seen the cost of molecular testing decrease by orders of magnitude. In 2018, we saw the first “site-agnostic” drug approvals in cancer (for microsatellite unstable cancer (PD-1 inhibitors) and NTRK-fusions (TRK inhibitors)). Research on targetable mutations, determination of genetic “signatures” that can use multiple individual genes/pathways, development of targeted therapy, and insight into the value of new technology remains at the cutting edge of research in this field. We are soliciting papers that present new technologies to assess predictive biomarkers in cancer, original research (pre-clinical or clinical) that demonstrates promise for particular targeted therapies in cancer, and articles that explore the clinical and financial impacts of this paradigmatic shift in cancer diagnostics and treatment.
Download or read book Holland Frei Cancer Medicine written by Robert C. Bast, Jr. and published by John Wiley & Sons. This book was released on 2017-03-10 with total page 2004 pages. Available in PDF, EPUB and Kindle. Book excerpt: Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates
Download or read book Folate Antagonists as Therapeutic Agents written by F. M. Sirotnak and published by . This book was released on 1984 with total page 388 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book How Tobacco Smoke Causes Disease written by United States. Public Health Service. Office of the Surgeon General and published by . This book was released on 2010 with total page 728 pages. Available in PDF, EPUB and Kindle. Book excerpt: This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.
Download or read book New anti cancer strategies targeting epigenetic modifications and associated metabolism reprogramming written by Lixiang Xue and published by Frontiers Media SA. This book was released on 2023-07-05 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Strategies for Overcoming Chemotherapy Resistance in Cervical Cancer written by Zodwa Dlamini and published by Elsevier. This book was released on 2024-01-23 with total page 218 pages. Available in PDF, EPUB and Kindle. Book excerpt: Strategies for overcoming chemotherapy resistance in cervical cancer highlights different strategies to reverse chemotherapy resistance in cervical cancer. The book has a strong focus on strategies to reverse chemotherapy resistance as well as strategies for early detection of the resistance, enhancing precision oncology in terms of patient care and maximizing patient management. The book also looks at virally induced resistance to chemotherapy and recommends combination therapies that can maximize the reversal of this resistance. In 10 chapters Strategies for overcoming chemotherapy resistance in cervical cancer not only gives an overview of cervical cancer and chemotherapy as treatment, but it also investigates resistance to chemotherapy and the treatment for resistance. It defines the treatment mechanisms, options, and limitations to beat chemotherapy resistance and the reversal of the resistance mechanisms. It gives insights into the future directions of cervical cancer treatment using epigenetic silencing, chemotherapy splicing, the involvement of MicroRNAs to chemotherapy resistance, and the application of Artificial Intelligence. This book is a valuable resource for health professionals, scientists and researchers, oncologists, virologists, health practitioners, medical and graduate students, and all those who wish to broaden their knowledge in the allied field. Discusses strategies to reverse and detect resistance to chemotherapy at an early stage Investigates the applications of Artificial Intelligence in the study of cervical chemotherapy resistance Presents research and applications developed to overcome cancer resistance
Download or read book Epigenetic Therapy of Cancer written by Michael Lübbert and published by Springer Science & Business Media. This book was released on 2013-12-12 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: The growing knowledge about disturbances of epigenetic gene regulation in hematopoietic stem cell disorders is now being translated into treatment approaches that target the epigenetic defects pharmacologically. This book first presents the latest evidence regarding the epigenetic regulation of hematopoietic stem cell differentiation and hemoglobin production. The significance of DNA methylation abnormalities in hematopoietic disorders and of epigenetic disturbances in lung cancer and other solid tumors is then discussed. A major part of the book, however, relates specifically to the translation of basic research and drug development to clinical applications, and in this context both present and future clinical strategies are considered. Individual chapters are devoted to the use of DNA hypomethylating agents and chromatin-modifying agents, and the treatment of hematologic malignancies and solid tumors by means of epigenetic agents is discussed in detail.
Download or read book Special Issue on Innovative Multi Disciplinary Approaches for Precision Studies in Leukemia written by Xu Huang and published by Frontiers Media SA. This book was released on 2021-10-01 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Insulin Like Growth Factors in Development Cancers and Aging written by Haim Werner and published by MDPI. This book was released on 2021-08-30 with total page 196 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Special Issue of Cells on “Insulin-Like Growth Factors in Development, Cancers and Aging” provides a collection of modern articles dealing with the role of insulin-like growth factors (IGF1) in cancer biology, aging and development. Featured articles explore basic and clinical aspects of the IGF1 system, including post-genomic analyses as well as novel approaches to target the IGF1 receptor (IGF1R) in oncology.
Download or read book Innovations for Next Generation Antibody Drug Conjugates written by Marc Damelin and published by Springer. This book was released on 2018-05-29 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: Antibody-drug conjugates (ADCs) stand at the verge of a transformation. Scores of clinical programs have yielded only a few regulatory approvals, but a wave of technological innovation now empowers us to overcome past technical challenges. This volume focuses on the next generation of ADCs and the innovations that will enable them. The book inspires the future by integrating the field’s history with novel strategies and cutting-edge technologies. While the book primarily addresses ADCs for solid tumors, the last chapter explores the emerging interest in using ADCs to treat other diseases. The therapeutic rationale of ADCs is strong: to direct small molecules to the desired site of action (and away from normal tissues) by conjugation to antibodies or other targeting moieties. However, the combination of small and large molecules imposes deep complexity to lead optimization, pharmacokinetics, toxicology, analytics and manufacturing. The field has made significant advances in all of these areas by improving target selection, ADC design, manufacturing methods and clinical strategies. These innovations will inspire and educate scientists who are designing next-generation ADCs with the potential to transform the lives of patients.
Download or read book Killing Cancer written by Tuula Kallunki and published by MDPI. This book was released on 2020-11-17 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite the efficiency of current cancer treatments, cancer is still a deadly disease for too many. In 2008, 7.6 million people died of cancer; with the current development, it is estimated that the annual cancer death number will grow to 13 million by 2030. There is clearly a need for not only more research but also more innovative and out of the mainstream scientific ideas to discover and develop even better cancer treatments. This book presents the collective works published in the recent Special Issue entitled “Killing Cancer: Discovery and Selection of New Target Molecules”. These articles comprise a selection of studies, ideas, and opinions that aim to facilitate knowledge, thoughts, and discussion about which biological and molecular mechanisms in cancer we should target and how we should target them.
Download or read book Theranostics Approaches to Gastric and Colon Cancer written by Ganji Seeta Rama Raju and published by Springer Nature. This book was released on 2020-03-04 with total page 261 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book highlights the importance of understanding gastric and colon cancer metabolism in guiding diagnosis and drug discovery. It summarizes the correlation between adiponectin and matrix metalloproteinase with colorectal cancer. The book also evaluates the divergent role of hypoxia-inducible factor 1 in colorectal cancer growth and metastasis. After discussing the role of genetic polymorphisms in alcohol metabolizing enzymes and EPHX1 with the onset of colorectal cancer, it reviews the molecular mechanisms of chemoresistance in gastric cancer and novel therapeutic strategies to reverse the chemoresistance of tumors. In addition, the book explores the theranostic role of nanoparticles and therapeutic potential of phytochemicals with regard to colorectal cancer. Given its scope, the book offers a valuable guide for oncologists, academic researchers, pharmaceuticals practitioners, and students who are involved in research and treatment of cancer.
