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Self Eating On Demand Autophagy In Cancer And Cancer Therapy
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Book Synopsis Self-Eating on Demand: Autophagy in Cancer and Cancer Therapy by : Patrizia Agostinis
Download or read book Self-Eating on Demand: Autophagy in Cancer and Cancer Therapy written by Patrizia Agostinis and published by Frontiers Media SA. This book was released on 2018-02-19 with total page 111 pages. Available in PDF, EPUB and Kindle. Book excerpt: Macroautophagy, the major lysosomal pathway for recycling intracellular components including whole organelles, has emerged as a key process modulating tumorigenesis, tumor–stroma interactions, and cancer therapy. An impressive number of studies over the past decade have unraveled the plastic role of autophagy during tumor development and dissemination. The discoveries that autophagy may either support or repress neoplastic growth and contextually favor or weaken resistance and impact antitumor immunity have spurred efforts from many laboratories trying to conceptualize the complex role of autophagy in cancer using cellular and preclinical models. This complexity is further accentuated by recent findings highlighting that various autophagy-related genes have roles beyond this catabolic mechanism and interface with oncogenic pathways, other trafficking and degradation mechanisms and the cell death machinery. From a therapeutic perspective, knowledge of how autophagy modulates the tumor microenvironment is crucial to devise autophagy-targeting strategies using smart combination of drugs or anticancer modalities. This eBook contains a collection of reviews by autophagy researchers and provides a background to the state-of-the-art in the field of autophagy in cancer, focusing on various aspects of autophagy regulation ranging from its molecular components to its cell autonomous role, e.g. in cell division and oncogenesis, miRNAs regulation, cross-talk with cell death pathways as well as cell non-autonomous role, e.g. in secretion, interface with tumor stroma and clinical prospects of autophagy-based biomarkers and autophagy modulators in anticancer therapy. This eBook is part of the TransAutophagy initiative to better understand the clinical implications of autophagy in cancer.
Book Synopsis Self-Eating on Demand: Autophagy in Cancer and Cancer Therapy by :
Download or read book Self-Eating on Demand: Autophagy in Cancer and Cancer Therapy written by and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Macroautophagy, the major lysosomal pathway for recycling intracellular components including whole organelles, has emerged as a key process modulating tumorigenesis, tumor-stroma interactions, and cancer therapy. An impressive number of studies over the past decade have unraveled the plastic role of autophagy during tumor development and dissemination. The discoveries that autophagy may either support or repress neoplastic growth and contextually favor or weaken resistance and impact antitumor immunity have spurred efforts from many laboratories trying to conceptualize the complex role of autophagy in cancer using cellular and preclinical models. This complexity is further accentuated by recent findings highlighting that various autophagy-related genes have roles beyond this catabolic mechanism and interface with oncogenic pathways, other trafficking and degradation mechanisms and the cell death machinery. From a therapeutic perspective, knowledge of how autophagy modulates the tumor microenvironment is crucial to devise autophagy-targeting strategies using smart combination of drugs or anticancer modalities. This eBook contains a collection of reviews by autophagy researchers and provides a background to the state-of-the-art in the field of autophagy in cancer, focusing on various aspects of autophagy regulation ranging from its molecular components to its cell autonomous role, e.g. in cell division and oncogenesis, miRNAs regulation, cross-talk with cell death pathways as well as cell non-autonomous role, e.g. in secretion, interface with tumor stroma and clinical prospects of autophagy-based biomarkers and autophagy modulators in anticancer therapy. This eBook is part of the TransAutophagy initiative to better understand the clinical implications of autophagy in cancer.
Book Synopsis Targeting Autophagy in Cancer Therapy by : Jin-Ming Yang
Download or read book Targeting Autophagy in Cancer Therapy written by Jin-Ming Yang and published by Springer. This book was released on 2016-09-02 with total page 146 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume will detail the current state and perspectives of autophagy-based cancer therapy. Covering a wide range of topics, it will include an overview of autophagy as a therapeutic target in cancer, autophagy modulators as cancer therapeutic agents, implications of micro-RNA-regulated autophagy in cancer therapy, modulation of autophagy through targeting PI3 kinase in cancer therapy, targeting autophagy in cancer stem cells, and roles of autophagy in cancer immunotherapy. In addition, the volume will review applications of system biology and bioinformatics approaches to discovering cancer therapeutic targets in the autophagy regulatory network. The volume will be beneficial for a variety of basic and clinical scientists, including cancer biologists, autophagy researchers, pharmacologists, and clinical oncologists who wish to delve more deeply into this field of cancer research. This volume will be the first book to focus solely on autophagy as a target in cancer therapy. As well, it will comprehensively discuss the roles of autophagy in most currently available cancer treatments.
Book Synopsis AUTOPHAGY AND CANCER by : Christopher Dower
Download or read book AUTOPHAGY AND CANCER written by Christopher Dower and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: A solid cancerous tumor is a complex mixture of many different cell types, varying compositions of extracellular matrix, and fluctuating degrees of oxygen and nutrient availability. This heterogeneity generates distinct stress-inducing tumor microenvironments (TME) that add selective pressure on cancer cells, selecting aggressive cancer cells that have an advantage of survival or metastatic potential. To survive stressful TMEs, cancer cells utilize an evolutionary conserved intracellular degradation and recycling mechanism, called autophagy (from the Greek for self-eating). Autophagy uses double membraned vesicles, called autophagosomes, to engulf cytoplasmic cargo for delivery to the lysosome for degradation. In general, autophagy is thought to promote cancer cell survival by facilitating the degradation of various cytoplasmic components and recycling of essential nutrients in starvation conditions, making it an attractive therapeutic strategy for treating cancers. However, the precise role of autophagy within the TME is controversial, as it exhibits both tumor-promoting and tumor-suppressing phenotypes, making it difficult to conclude whether autophagy is a viable target for cancer therapy. In particular, this paradox is most evident in regards to the role of autophagy in regulating cancer metastasis, as reports conflict as to whether autophagy is truly a metastasis-suppressing or -promoting pathway. Emerging research indicates that the influence of autophagy on cancer progression is dependent on several factors, including cancer cell type and the TME. Thus, more physiologically relevant assessments which incorporate TME-associated stress and cell-to-cell interactions are needed to better understand the role of autophagy in tumor progression. Accordingly, the primary focus of this doctoral dissertation involves elucidating the role of autophagy in tumor progression in the context of hypoxia (i.e. low oxygen conditions), a hallmark of the TME. In chapter 2, we explored the impact of autophagy on the pathophysiology of breast cancer cells, using a novel hypoxia-dependent, reversible dominant negative strategy to regulate autophagy at the cellular level within the TME. Suppression of autophagy via hypoxia-induced expression of the kinase-dead dominant-negative mutant of ULK1 (dnULK1K49R) increased lung metastases in MDA-MB-231 xenograft mouse models. Consistent with this effect, expressing a dominant-negative mutant of ULK1 or ATG4b or a ULK1-targeting shRNA facilitated cell migration in vitro. Functional proteomic and transcriptome analysis revealed that loss of hypoxia-regulated autophagy promotes metastasis via induction of the fibronectin integrin signaling axis. In agreement, loss of ULK1 function increased fibronectin deposition in the hypoxic TME. Additionally, we report that low expression of autophagy genes predicts a worse prognosis in human breast cancer. Together, our results indicated that hypoxia-regulated autophagy suppresses metastasis in breast cancer by preventing tumor fibrosis. These results also suggest caution in the development of autophagy-based strategies for cancer treatment. In addition to this, a secondary focus of this dissertation involved examining the translational implications of targeting autophagy for therapeutic benefit in neuroblastoma, a cancer of immature nerve cells that predominantly effects children under five years old. In chapter 3, we demonstrate that targeted inhibition of an essential autophagy kinase, ULK1, with a recently developed small molecular inhibitor of ULK1, SBI-0206965, significantly reduces cell growth and promotes apoptosis in SK-N-AS, SH-SY5Y, and SK-N-DZ neuroblastoma cell lines. Furthermore, inhibition of ULK1 by a dominant-negative mutant of ULK1 (dnULK1K49R) significantly reduced growth and metastatic disease and prolonged survival of mice bearing SK-N-AS xenograft tumors. We also show that SBI-0206965 sensitized SK-N-AS cells to TRAIL treatment, but not mTOR inhibitors (INK128, Torin1) or topoisomerase inhibitors (doxorubicin, topotecan). Collectively, these findings demonstrate that ULK1 is a viable drug target and inhibitors of ULK1 may provide a novel therapeutic option for the treatment of neuroblastoma. Furthermore, this work demonstrates the antitumor effects of targeting an essential autophagy gene in neuroblastoma mouse models.In summation, this dissertation has elucidated that hypoxia-regulated autophagy acts to suppress metastasis in breast cancer, and demonstrated that ULK1 kinase is a viable drug target for the treatment of neuroblastoma. Collectively, this work has further defined the complex role of autophagy in tumor biology, as well as provided pre-clinical data that may aid in the development of novel treatment options for cancer patients.
Book Synopsis Autophagy and Cancer by : Hong-Gang Wang
Download or read book Autophagy and Cancer written by Hong-Gang Wang and published by Springer Science & Business Media. This book was released on 2013-03-30 with total page 267 pages. Available in PDF, EPUB and Kindle. Book excerpt: With the explosion of information on autophagy in cancer, this is an opportune time to speed the efforts to translate our current knowledge about autophagy regulation into better understanding of its role in cancer. This book will cover the latest advances in this area from the basics, such as the molecular machinery for autophagy induction and regulation, up to the current areas of interest such as modulation of autophagy and drug discovery for cancer prevention and treatment. The text will include an explanation on how autophagy can function in both oncogenesis and tumor suppression and a description of its function in tumor development and tumor suppression through its roles in cell survival, cell death, cell growth as well as its influences on inflammation, immunity, DNA damage, oxidative stress, tumor microenvironment, etc. The remaining chapters will cover topics on autophagy and cancer therapy. These pages will serve as a description on how the pro-survival function of autophagy may help cancer cells resist chemotherapy and radiation treatment as well as how the pro-death functions of autophagy may enhance cell death in response to cancer therapy, and how to target autophagy for cancer prevention and therapy − what to target and how to target it.
Book Synopsis Role of Autophagy in Cancer by : Hsin-Yi Chen
Download or read book Role of Autophagy in Cancer written by Hsin-Yi Chen and published by . This book was released on 2011 with total page 128 pages. Available in PDF, EPUB and Kindle. Book excerpt: (Macro)autophagy is a catabolic process whereby intracellular components are enclosed into autophagosomes and delivered to lysosomes for degradation. Constitutive activity of autophagy contributes to turnover of proteins and organelles, ensuring the quality control of cellular components. Autophagy also can be induced by starvation or other stresses. This activity serves to provide internal resources to sustain metabolism and to prevent accumulation of detrimental substances. Therefore, autophagy is critical for cells to maintain homeostasis and to survive stress. Tumors are often subjected to metabolic stress due to insufficient vascularization. Autophagy is induced and localizes to these hypoxic regions where it supports survival. In aggressive tumors, the increased metabolic demand of rapid proliferation and growth may augment the dependency of cells on autophagy. In addition, autophagy that is induced by cancer therapy may be utilized by tumor cells for survival and be counterproductive to therapeutic efficacy. In this work, we tested the hypothesis that autophagy enables tumor cell survival and tumorigenesis in two different settings and addressed the underlying mechanism by which this occurs. First, we demonstrated that autophagy is required for viability in starvation and tumorigenicity of cells with oncogenic Ras activation. In these cells, defective autophagy caused abnormal mitochondria accumulation and reduced mitochondrial functionality in starvation associated with reduced energy charge. Since mitochondrial function is required for survival during starvation, we reasoned that autophagy supports survival and tumorigenicity of Ras-expressing cells by maintaining mitochondrial functionality. We also demonstrated that autophagy maintained mitochondrial function by preserving functional mitochondrial pools through mitophagy as well as by providing substrates for mitochondrial bioenergetic production under stress, thereby identifying autophagy and mitophagy as potential targets for treatment of cancers with oncogenic Ras activation. Second, we examined the significance of the mTOR inhibition-induced autophagy in counteracting the efficacy of the mTOR inhibitor CCI-779, which has shown temporary effectiveness in clinical treatment of human renal cell carcinoma. We demonstrated that mTOR inhibition promoted autophagy-mediated stress tolerance. Inhibition of autophagy with chloroquine enhanced the cytotoxicity of CCI-779 in vitro and in allograft tumors in mice. We further demonstrated that autophagy promoted cell survival in CCI-779-treated cells by providing alternative substrates for mitochondrial metabolism and suppressing reactive oxygen species production. This result justified a combination of autophagy inhibition with mTOR inhibitors in cancer therapy.
Book Synopsis Autophagy and Senescence in Cancer Therapy by : Paul B. Fisher
Download or read book Autophagy and Senescence in Cancer Therapy written by Paul B. Fisher and published by Elsevier. This book was released on 2021-04-15 with total page 382 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Cancer Research, Volume 150, the latest release in this ongoing series, covers the relationship(s) between autophagy and senescence, how they are defined, and the influence of these cellular responses on tumor dormancy and disease recurrence. Specific sections in this new release include Autophagy and senescence, converging roles in pathophysiology, Cellular senescence and tumor promotion: role of the unfolded protein response, autophagy and senescence in cancer stem cells, Targeting the stress support network regulated by autophagy and senescence for cancer treatment, Autophagy and PTEN in DNA damage-induced senescence, mTOR as a senescence manipulation target: A forked road, and more. Addresses the relationship between autophagy and senescence in cancer therapy Covers autophagy and senescence in tumor dormancy Explores autophagy and senescence in disease recurrence
Book Synopsis Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging by : M. A. Hayat
Download or read book Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging written by M. A. Hayat and published by Academic Press. This book was released on 2016-12-28 with total page 431 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. Presents the most advanced information regarding the role of the autophagic system in life and death Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available
Book Synopsis Autophagy in tumor and tumor microenvironment by : Sujit Kumar Bhutia
Download or read book Autophagy in tumor and tumor microenvironment written by Sujit Kumar Bhutia and published by Springer Nature. This book was released on 2020-10-24 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book deals with the paradoxical role of autophagy in tumor suppression and tumor promotion in cancer cells. Autophagy plays opposing, context-dependent roles in tumors; accordingly, strategies based on inhibiting or stimulating autophagy could offer as potential cancer therapies. The book elucidates the physiological role of autophagy in modulating cancer metastasis, which is the primary cause of cancer-associated mortality. Further, it reviews its role in the differentiation, development, and activation of multiple immune cells, and its potential applications in tumor immunotherapy. In addition, it examines the effect of epigenetic modifications of autophagy-associated genes in regulating tumor growth and therapeutic response and summarizes autophagy’s role in the development of resistance to a variety of anti-cancer drugs in cancer cells. In closing, it assesses autophagy as a potential therapeutic target for cancer treatment. Given its scope, the book offers a valuable asset for all oncologists and researchers who wish to understand the potential role of autophagy in tumor biology.
Book Synopsis Drug Targets in Cellular Processes of Cancer: From Nonclinical to Preclinical Models by : Hardeep Singh Tuli
Download or read book Drug Targets in Cellular Processes of Cancer: From Nonclinical to Preclinical Models written by Hardeep Singh Tuli and published by Springer Nature. This book was released on 2020-09-30 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book explores potential cellular drug targets for cancer therapy. The first couple of chapters describe conventional treatment (radiotherapy, chemotherapy, and immunotherapy) & detection (biosensors) strategies for cancer. In contrast, the subsequent chapters address the role of cyclin-dependent kinases and cell cycle regulatory proteins in the growth of cancer cells and their potential as target for cancer treatment. The book then discusses the regulation of various pro-apoptotic and anti-apoptotic proteins via chemotherapeutic drugs. In addition, it examines the molecular mechanisms that are critical for mediating autophagic cell death in cancer cells. It subsequently reviews the role of reactive oxygen (ROS) species during carcinogenesis and during chemotherapy, and the potential of anti-inflammatory routes for the development of new therapeutic modulators. Lastly, it describes therapeutic strategies that target the tumor microenvironment and various angiogenic pathways for the treatment of cancer and to develop personalized medicine. Given its scope, the book is valuable resource for oncologists, cancer researchers, clinicians, and pharmaceutical industry personnel.
Book Synopsis New Roles of Autophagy Pathways in Cancer by : Daniel Hector Grasso
Download or read book New Roles of Autophagy Pathways in Cancer written by Daniel Hector Grasso and published by Frontiers Media SA. This book was released on 2021-09-10 with total page 369 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging by : M. A. Hayat
Download or read book Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging written by M. A. Hayat and published by Academic Press. This book was released on 2017-09-07 with total page 624 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, Volume 12 discusses and details almost all aspects of the autophagy machinery in the context of health, cancer and other pathologies. Autophagy is more widely accepted as beneficial given its role in eliminating ‘toxic assets’ and promoting cell viability, hence, it has emerged as a new and potent modulator of disease progression that is both scientifically intriguing and clinically relevant. As the latest release in the Autophagy book series, users will find a detailed explanation of the role of molecular mechanisms. Presents the most advanced information regarding the role of the autophagic system in life and death States recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities Summarizes the most up-to-date findings on how autophagy is executed and regulated at the molecular level and how its disruption can lead to disease Authored by global leaders in the field, bringing the broadest, most expert coverage available
Book Synopsis Mitochondria and Cancer by : Keshav Singh
Download or read book Mitochondria and Cancer written by Keshav Singh and published by Springer Science & Business Media. This book was released on 2009-04-05 with total page 294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nearly a century of scientific research has revealed that mitochondrial dysfunction is one of the most common and consistent phenotypes of cancer cells. A number of notable differences in the mitochondria of normal and cancer cells have been described. These include differences in mitochondrial metabolic activity, molecular composition of mitochondria and mtDNA sequence, as well as in alteration of nuclear genes encoding mitochondrial proteins. This book, Mitochondria and Cancer, edited by Keshav K. Singh and Leslie C. Costello, presents thorough analyses of mitochondrial dysfunction as one of the hallmarks of cancer, discusses the clinical implications of mitochondrial defects in cancer, and as unique cellular targets for novel and selective anti-cancer therapy.
Book Synopsis Current Advances in Osteosarcoma by : Eugenie S. Kleinerman, M.D.
Download or read book Current Advances in Osteosarcoma written by Eugenie S. Kleinerman, M.D. and published by Springer. This book was released on 2016-08-23 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Current Advances in Osteosarcoma edited by Dr. Eugenie S. Kleinerman summarizes molecular and genetic characteristics, new therapeutic ideas, and biological characteristics that have been uncovered in the past 10 years. Osteosarcoma is an aggressive malignant neoplasm and it is also the most common histological form of bone cancer. It accounts for approximately 56% of new bone tumors, making it the most primary malignant bone tumor in children and adolescents. The lungs are the most common site of metastases and once osteosarcoma spreads to the lungs, it is very difficult to treat. To improve the outcome of this disease, the biology of osteosarcoma needs to be better understood. There are numerous investigators around the world who have made seminal discoveries about the important molecular pathways and genetic alterations that contribute to the development and metastases of osteosarcoma. Other investigators have proposed novel therapeutic strategies including some based on the molecular and genetic phenotype of the disease. Current Advances in Osteosarcoma summarizes all of these new discoveries in one singular text, which will help move the field forward.
Book Synopsis Autophagy - A Double-Edged Sword by : Yannick Bailly
Download or read book Autophagy - A Double-Edged Sword written by Yannick Bailly and published by BoD – Books on Demand. This book was released on 2013-04-17 with total page 526 pages. Available in PDF, EPUB and Kindle. Book excerpt: The chapters in this book review the latest advances in the molecular mechanisms of autophagy, highlighting some of the most challenging research topics. The focus is mainly on how this basic cell defense mechanism comes into play in various pathologies, including liver diseases, myopathies, infectious diseases, cancers and neurodegenerative diseases. In these diseases, the contradictory autophagy roles of cell survival versus cell death emphasize the necessity of taking into account this double-edged nature in future development of already promising, autophagy- modulating, therapies.
Book Synopsis Heat Shock Proteins in Cancer by : Stuart K. Calderwood
Download or read book Heat Shock Proteins in Cancer written by Stuart K. Calderwood and published by Springer Science & Business Media. This book was released on 2007-09-09 with total page 399 pages. Available in PDF, EPUB and Kindle. Book excerpt: Heat shock proteins are emerging as important molecules in the development of cancer and as key targets in cancer therapy. These proteins enhance the growth of cancer cells and protect tumors from treatments such as drugs or surgery. However, new drugs have recently been developed particularly those targeting heat shock protein 90. As heat shock protein 90 functions to stabilize many of the oncogenes and growth promoting proteins in cancer cells, such drugs have broad specificity in many types of cancer cell and offer the possibility of evading the development of resistance through point mutation or use of compensatory pathways. Heat shock proteins have a further property that makes them tempting targets in cancer immunotherapy. These proteins have the ability to induce an inflammatory response when released in tumors and to carry tumor antigens to antigen presenting cells. They have thus become important components of anticancer vaccines. Overall, heat shock proteins are important new targets in molecular cancer therapy and can be approached in a number of contrasting approaches to therapy.
Book Synopsis Metabolism in Cancer by : Thorsten Cramer
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.
