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PARP Inhibitors for Cancer Therapy

PARP Inhibitors for Cancer Therapy Author Nicola Curtin
ISBN-10 9783319141510
Release 2015-06-13
Pages 591
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PARP Inhibitors for Cancer Therapy provides a comprehensive overview of the role of PARP in cancer therapy. The volume covers the history of the discovery of PARP (poly ADP ribose polymerase) and its role in DNA repair. In addition, a description of discovery of the PARP family, and other DNA maintenance-associated PARPs will also be discussed. The volume also features a section on accessible chemistry behind the development of inhibitors. PARP inhibitors are a group of pharmacological inhibitors that are a particularly good target for cancer therapy. PARP plays a pivotal role in DNA repair and may contribute to the therapeutic resistance to DNA damaging agents used to treat cancer. Researchers have learned a tremendous amount about the biology of PARP and how tumour-specific defects in DNA repair can be exploited by PARPi. The “synthetic lethality” of PARPi is an exciting concept for cancer therapy and has led to a heightened activity in this area.



Targeting the DNA Damage Response for Anti Cancer Therapy

Targeting the DNA Damage Response for Anti Cancer Therapy Author John Pollard
ISBN-10 9783319758367
Release 2018-05-26
Pages 401
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Over the past decade a complex role for DNA damage response (DDR) in tumorigenesis has emerged. A proficient DDR has been shown to be a primary cause for cellular resistance to the very many DNA damaging drugs, and IR, that are widely used as standard-of-care across multiple cancer types. It has also been shown that defects in this network, predominantly within the ATM mediated signaling pathway, are commonly observed in cancers and may be a primary event during tumorigenesis. Such defects may promote a genomically unstable environment, facilitating the persistence of mutations, any of which may provide a growth or survival advantage to the developing tumor. In addition, these somatic defects provide opportunities to exploit a reliance on remaining repair pathways for survival, a process which has been termed synthetic lethality. As a result of all these observations there has been a great interest in targeting the DDR to provide anti-cancer agents that may have benefit as monotherapy in cancers with high background DNA damage levels or as a means to increase the efficacy of DNA damaging drugs and IR. In this book we will review a series of important topics that are of great interest to a broad range of academic, industrial and clinical researchers, including the basic science of the DDR, its role in tumorigenesis and in dictating response to DNA damaging drugs and IR. Additionally, we will focus on the several proteins that have been targeted in attempts to provide drug candidates, each of which appear to have quite distinct profiles and could represent very different opportunities to provide patient benefit.



Matrix Metalloproteinase Inhibitors in Cancer Therapy

Matrix Metalloproteinase Inhibitors in Cancer Therapy Author Neil J. Clendeninn
ISBN-10 9781592590117
Release 2000-09-17
Pages 262
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Cutting-edge investigators review the current status of the entire field, from the biology of MMPs through the current clinical studies. The authors include many leading scientists from pharmaceutical companies who present all the latest concepts and results on the preferred design strategies for MMP inhibitors, their molecular mechanisms, and their substrates. In addition, they fully describe their personal research on specific MMP inhibitors, detailing vanguard design strategies, their in vitro activity, the outcome of animal model studies and, where available, their toxicology, safety, efficacy in human clinical trials. Comprehensive and state-of-the-art, Matrix Metalloproteinase Inhibitors in Cancer Therapy offers basic and clinical investigators alike a richly informative summary of all the latest research on these powerful new drugs, and their high promise as emerging cancer therapeutics.



DNA Repair in Cancer Therapy

DNA Repair in Cancer Therapy Author Mark R. Kelley
ISBN-10 9780123849991
Release 2012
Pages 316
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Cancer therapeutics include an ever-increasing array of tools at the disposal of clinicians in their treatment of this disease. However, cancer is a tough opponent in this battle, and current treatments, which typically include radiotherapy, chemotherapy and surgery, are not often enough to rid the patient of his or her cancer. Cancer cells can become resistant to the treatments directed at them, and overcoming this drug resistance is an important research focus. Additionally, increasing discussion and research is centering on targeted and individualized therapy. While a number of approaches have undergone intensive and close scrutiny as potential approaches to treat and kill cancer (signaling pathways, multidrug resistance, cell cycle checkpoints, anti-angiogenesis, etc.), other approaches have focused on blocking the ability of a cancer cell to recognize and repair the damaged DNA that primarily results from the front-line cancer treatments; chemotherapy and radiation. This comprehensive and timely reference focuses on the translational and clinical use of DNA repair as a target area for the development of diagnostic biomarkers and the enhancement of cancer treatment. Saves academic, medical, and pharmaceutical researchers time in quickly accessing the very latest details on DNA repair and cancer therapy, as opposed to searching through thousands of journal articles Provides a common language for cancer researchers, oncologists, and radiation oncologists to discuss their understanding of new molecular pathways, clinical targets, and anti-cancer drug development Provides content for researchers and research clinicians to understand the importance of the breakthroughs that are contributing to advances in disease-specific research



Advances in DNA Repair in Cancer Therapy

Advances in DNA Repair in Cancer Therapy Author Lawrence Panasci
ISBN-10 9781461447412
Release 2012-12-09
Pages 312
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​A comprehensive review of the recent developments in DNA repair research that have potential for translational applications. The book explains in detail the various biological mechanisms by which cancer cells can circumvent anticancer therapy and limits its usefulness in patients. They also review the impact of such novel inhibitors of DNA repair mechanisms as methylguanine-DNA-methyltransferase. Also examined are inhibitors of other DNA repair enzymes such as PARP and DNA-PK. The book captures-for both cancer researchers and oncologists dealing with hallmark "relapse" or "drug resistance" phenomena on a daily basis-the many exciting new uses of DNA repair inhibitors, either alone or in combination with anticancer therapies.​



Neurologic Complications of Cancer Therapy

Neurologic Complications of Cancer Therapy Author Eudocia Quant Lee, MD, MPH
ISBN-10 9781617050190
Release 2011-09-28
Pages 200
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Neurologic side effects of cancer therapy can inhibit treatment, can be dose-limiting and can diminish quality-of-life. Neurotoxicity related to cancer therapy is a common problem in oncology practice and in clinical neurology. Recognition of neurologic complications of anticancer therapy is necessary due to potential confusion with metastatic disease, paraneoplastic syndromes or comorbid neurologic disorders that do not require reduction or discontinuation of therapy. Neurologic Complications of Cancer Therapy provides comprehensive coverage of the recognition and management of neurologic symptoms related to cancer therapy. The book includes sections on systemic therapy discussed by both agent and adverse event. The section on adverse events is particularly valuable to clinicians, allowing them to consult by symptom in cases where multiple agents have been administered and the source of the complication is uncertain. The systemic therapy section includes coverage of immunologic agents, biologics, and targeted therapies. The book also features sections on the complications of radiation therapy, complications of surgery and high-dose chemotherapy, and stem cell transplantation. Neurologic Complications of Cancer Therapy Features: A widely recognized team of editors Systemic therapy covered by therapeutic agent and by adverse event, enabling a "problem-oriented" approach for the clinician Coverage of newer modalities including immunologic agents, biologics, and targeted therapies Complete sections on complications of radiation therapy, surgery, high-dose chemotherapy, and stem-call transplantion



DNA Repair in Cancer Therapy

DNA Repair in Cancer Therapy Author Lawrence C. Panasci
ISBN-10 9781592597352
Release 2004-03-19
Pages 363
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A comprehensive review of the recent developments in DNA repair that have potential for translational and clinical applications. The authors explain in detail the various mechanisms by which cancer cells can circumvent anticancer therapy and limits its usefulness in patients. They also review the clinical impact of such novel inhibitors of DNA repair mechanisms as methylguanine-DNA-methyltransferase. Also examined are inhibitors of other DNA repair enzymes such as PARP and DNA-PK, now under development and close to clinical trials. The book captures-for both cancer researchers and practicing oncologists dealing with hallmark "relapse" or "drug resistance" phenomena on a daily basis-the many exciting new uses of DNA repair inhibitors, either alone or in combination with anticancer therapies.



Inhibiting PARP as a Strategic Target in Cancer

Inhibiting PARP as a Strategic Target in Cancer Author Christina Annunziata
ISBN-10 9782889199556
Release 2016-08-05
Pages
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Poly-ADP ribose polymerase (PARP) proteins are critical mediators of DNA repair. Many traditional anti-cancer chemotherapy agents overwhelm a cell’s ability to repair DNA damage in order to kill proliferating malignant cells. Recent evidence suggests that cancers within and across tissue types have specific defects in DNA repair pathways, and that these defects may predispose for sensitivity and resistance to various classes of cytotoxic agents. Breast, ovarian and other cancers develop in the setting of inherited DNA repair deficiency, and these cancers may be more sensitive to cytotoxic agents that induce DNA strand breaks, as well as to inhibitors of PARP activity. A series of recent clinical trials has tested whether PARP inhibitors can achieve synthetic lethality in hereditary DNA repair-deficient tumors. At the current time, mutation of BRCA serves as a potential, but not comprehensive, biomarker to predict response to PARP inhibitor therapy. Mechanisms of resistance to PARP inhibitors are only recently being uncovered. Future studies seek to identify sporadic cancers that harbor genomic instability rendering susceptibility to PARP inhibitors that compound lethal DNA damage.



The Molecular Basis of Human Cancer

The Molecular Basis of Human Cancer Author William B. Coleman
ISBN-10 9781597454582
Release 2016-11-11
Pages 873
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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.



Cancer Drug Design and Discovery

Cancer Drug Design and Discovery Author Stephen Neidle
ISBN-10 9780123972286
Release 2013-09-30
Pages 640
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Cancer Drug Design and Discovery, Second Edition is an important reference on the underlying principles for the design and subsequent development of new anticancer small molecule agents. New chapters have been added to this edition on areas of particular interest and therapeutic promise, including cancer genomics and personalized medicine, DNA-targeted agents and more. This book includes several sections on the basic and applied science of cancer drug discovery and features those drugs that are now approved for human use and are in the marketplace, as well as those that are still under development. By highlighting some of the general principles involved in taking molecules through basic science to clinical development, this book offers a complete and authoritative reference on the design and discovery of anticancer drugs for translational scientists and clinicians involved in cancer research. Provides a clinical perspective on the development of new molecularly targeted anticancer agents with the latest and most promising chemotherapeutic approaches Offers a broad view of where the field is going, what tools drug discovery is using to produce new agents and how they are evaluated in the laboratory and clinic Features 6 new chapters devoted to advances in technology and successful anticancer therapies, such as cancer genomics and personalized medicine, DNA-targeted agents, B-Raf inhibitors and more Each chapter includes extensive references to the primary and review literature, as well as to relevant web-based sources



Handbook of Anticancer Pharmacokinetics and Pharmacodynamics

Handbook of Anticancer Pharmacokinetics and Pharmacodynamics Author Michelle A. Rudek
ISBN-10 9781461491354
Release 2014-01-10
Pages 836
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There are many steps on the road from discovery of an anticancer drug to securing its final approval by the Food and Drug Administration. In this thoroughly updated and expanded second edition of the Handbook of Anticancer Pharmacokinetics and Pharmacodynamics, leading investigators synthesize an invaluable overview of the experimental and clinical processes of anticancer drug development, creating a single indispensable reference that covers all the steps from the identification of cancer-specific molecular targets to screening techniques and the development and validation of bioanalytical methods to clinical trial design and all phases of clinical trials. The authors have included new material on phase 0 trials in oncology, organ dysfunction trials, drug formulations and their impact on anticancer drug PK/PD including strategies to improve drug delivery, pharmacogenomics and cancer therapy, high throughput platforms in drug metabolism and transport pharmacogenetics, imaging in drug development and nanotechnology in cancer. Authoritative and up-to-date, Handbook of Anticancer Pharmacokinetics and Pharmacodynamics, 2nd Edition provides in one comprehensive and highly practical volume a detailed step-by-step guide to the successful design and approval of anticancer drugs. Road map to anticancer drug development from discovery to NDA submission Discussion of molecular targets and preclinical screening Development and validation of bioanalytical methods Chapters on clinical trial design and phase 0, I, II, III clinical trials Pharmacokinetics, pharmacodynamics, pharmacogenomics, and pharmacogenetics of anticancer agents Review of the drug development process from both laboratory and clinical perspectives New technological advances in imaging, high throughput platforms, and nanotechnology in anticancer drug development



PI3K mTOR in Cancer and Cancer Therapy

PI3K mTOR in Cancer and Cancer Therapy Author Nandini Dey
ISBN-10 9783319342115
Release 2016-06-10
Pages 294
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In the post human-genome project era, cancer specific genomic maps are redesigning tumor taxonomy by evolving from histopathology to molecular pathology. The success of a cancer drug today is fundamentally based on the success in identifying target genes that control beneficial pathways. The overwhelming power of genomics and proteomics has enlightened researchers about the fact that the PI3K-mTOR pathway is the most commonly up-regulated signal transduction pathway in various cancers, either by virtue of its activation downstream of many cell surface growth factor receptors or by virtue of its collateral and compensatory circuitry with RAS-MAPK pathway. Oncogenic signaling in the majority of solid tumors is sustained via the PI3K-AKT-mTOR pathway. Because of its prominent role in many cancer types, the PI3K-mTOR pathway has become a major therapeutic target. The volume includes two complementary parts which address the problem of etiology and disease progression and is intended to portray the very basic mechanisms of the PI3K-AKT-mTOR signaling pathway’s involvement in various facets of the cancer, including stem cell renewal, cell metabolism, angiogenesis, genetic instability, and drug resistance. Significant progress has been made in recent years elucidating the molecular mechanism of cancer cell proliferation, angiogenesis, and drug-resistance in relation to the PI3K-mTOR pathway and this volume provides an in-depth overview of recent developments made in this area.​



New Drugs for Malignancy An Issue of Hematology Oncology Clinics of North America E Book

New Drugs for Malignancy  An Issue of Hematology Oncology Clinics of North America   E Book Author Franco Muggia
ISBN-10 9781455744084
Release 2012-05-08
Pages 1440
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Topics include: Targeting IGF-1R, Tyrosine Kinase Inhibitors in Lung Cancer, Targeting mTOR, Targeting Hedgehog, Mitotic Inhibitors, Topoisomerase I Inhibitors , and New Strategies and Drugs Inhibiting Folate Pathways.



Neuroanatomy and Pathology of Sporadic Alzheimer s Disease

Neuroanatomy and Pathology of Sporadic Alzheimer s Disease Author Heiko Braak
ISBN-10 9783319126791
Release 2014-12-11
Pages 162
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As indicated by its title, this monograph deals chiefly with morphologically recognizable deviations from the normal anatomical condition of the human CNS. The AD-associated pathology is illustrated from its beginnings (sometimes even in childhood) to its final form, which is reached late in life. The AD process commences much earlier than the clinically recognizable phase of the disorder, and its timeline includes an extended preclinical phase. The further the pendulum swings away from the symptomatic final stages towards the early pathology, the more obvious the lesions become, although from a standpoint of severity they are more unremarkable and thus frequently overlooked during routine neuropathological assessment. For this reason, the authors deal with the hallmark lesions in the early phases of the AD process in considerable detail



Targeted Therapy in Translational Cancer Research

Targeted Therapy in Translational Cancer Research Author Apostolia-Maria Tsimberidou
ISBN-10 9781118468579
Release 2015-12-21
Pages 400
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Translational medicine has opened the gateway to the era of personalized medicine. No longer a one-size-fits-all approach, the treatment of cancer is now based on an understanding of underlying biologic mechanisms and is increasingly being tailored to the molecular specificity of a tumor. Translational Oncology: Targeted Therapy in Translational Cancer Research provides a comprehensive overview of the pertinent molecular discoveries in the cancer field and explains the clinical ramifications and utility of these on targeted cancer therapies. Beginning with a chapter introducing the “Bench to Bedside and Back” paradigm, an overview is presented of the exponential growth in the field of translational medicine, including historical perspectives and recent progress. Following the introduction, subsequent chapters review the progress of targeted therapy within three major categories: hematological malignancies, solid tumors, and hereditary cancers. Each of these categories comprises a single a chapter with subsections that discuss specific cancer types. Following this is a chapter on targeted and functional imaging that reviews progress in the different modalities of anatomical and molecular imaging used to complement targeted therapy. The next chapter discusses the need to combine individual agents with existing therapies or in novel combinations in order to overcome drug resistance. Following this is a chapter presenting the challenges in drug development and the selection of targets for cancer therapeutics. The final chapter offers perspectives on personalized medicine and presents future challenges in the investigation of optimal combinations and the identification of biomarkers that can provide both predictive and prognostic information for tailoring targeted therapies to individual patients.



The Development of PARP as a Successful Target for Cancer Therapy

The Development of PARP as a Successful Target for Cancer Therapy Author
ISBN-10 OCLC:1028202836
Release 2018
Pages
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ABSTRACT: Introduction : PARP1 and BRCA genes are essential genome caretakers and their interaction has been the first example of synthetic lethality, a genetic concept proposed in the early 20th century, but deeply explored in cancer patients only in the last decade. Areas covered : This review describes PARP1 and BRCA main functions and different roles in genome protection. Furthermore, an overview of the principle mechanisms of action and resistance to PARP inhibitors (PARPi) is presented. This review illustrates the concept of BRCAness, and how this discovery has broadened the routes of PARPi to several different malignancies such as ovarian, breast and prostate cancer. Finally, an insight is provided into the key data of PARPi in these distinctive clinical settings. Expert commentary : PARP inhibition could be a new therapeutic option for a number of tumors in the near future. However, several aspects will be of paramount interest for future investigations, including the molecular bases for PARPi synthetic lethality, the DNA repair independent functions of PARP and BRCA genes, the resistance and biomarkers of response to PARP inhibition, and the mechanisms of interaction between PARPi and antiangiogenic or immunotherapeutic agents.



Henry Kaplan and the Story of Hodgkin s Disease

Henry Kaplan and the Story of Hodgkin s Disease Author Charlotte Jacobs
ISBN-10 080477448X
Release 2010-04-28
Pages 456
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In the 1950s, ninety-five percent of patients with Hodgkin's disease, a cancer of lymph tissue which afflicts young adults, died. Today most are cured, due mainly to the efforts of Dr. Henry Kaplan. Henry Kaplan and the Story of Hodgkin's Disease explores the life of this multifaceted, internationally known radiation oncologist, called a "saint" by some, a "malignant son of a bitch" by others. Kaplan's passion to cure cancer dominated his life and helped him weather the controversy that marked each of his innovations, but it extracted a high price, leaving casualties along the way. Most never knew of his family struggles, his ill-fated love affair with Stanford University, or the humanitarian efforts that imperiled him. Today, Kaplan ranks as one of the foremost physician-scientists in the history of cancer medicine. In this book Charlotte Jacobs gives us the first account of a remarkable man who changed the face of cancer therapy and the history of a once fatal, now curable, cancer. She presents a dual drama —the biography of this renowned man who called cancer his "Moby Dick" and the history of Hodgkin's disease, the malignancy he set out to annihilate. The book recounts the history of Hodgkin's disease, first described in 1832: the key figures, the serendipitous discoveries of radiation and chemotherapy, the improving cure rates, the unanticipated toxicities. The lives of individual patients, bold enough to undergo experimental therapies, lend poignancy to the successes and failures. Visit the author's website.