Checkpoint Controls And Targets In Cancer Therapy
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Checkpoint Controls And Targets In Cancer Therapy
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Author : Zahid H. Siddik
language : en
Publisher: Springer Science & Business Media
Release Date : 2010-03-12
Checkpoint Controls And Targets In Cancer Therapy written by Zahid H. Siddik and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-03-12 with Medical categories.
Much work over the last two decades has firmly established that loss of cell cycle checkpoint regulation, and resultant unabated cellular proliferation, is an inherent characteristic of cancer. This loss may occur through aberration in any single component involved in signal transduction pathways that orchestrate checkpoint regulation, which may manifest through either a failure to activate the checkpoint or a failure to respond to the activated checkpoint. In normal cells, checkpoint pathways are activated when genetic or cellular homeostasis is compromised, and signals are then transduced to re-stabilize homeostasis, and, failing this, to activate the apoptotic machinery to induce a cellular suicidal response. This implies that both survival and cell death pathways are induced following checkpoint activation, and that the final decision is dependant on the net result of integrating the two sets of signals. It is intriguing that checkpoint pathways are also critical in cancer therapy to provide an apoptotic stimulus when cellular damage induced by the therapeutic agent is detected by the sensor system. Therefore, it is not surprising that failure in pro-survival checkpoint response will render tumor cells hypersensitive to cytotoxics and, conversely, failure in pro-apoptotic checkpoint response will induce genetic instability and/or therapeutic resistance. Understanding the intricacies of checkpoint response is, therefore, central to the design of therapeutic regimen that will enhance antitumor effects. Although early versions of this design entail combination of cytotoxic agents with cell cycle or checkpoint inhibitors, a greater understanding of the concepts could make such combinations clinically more effective. The contributions in this book will consolidate the current state of knowledge on checkpoint responses that may lay the foundation for hypothesis-driven rational approaches in advancing the management of cancer. The immediate attraction of the book to the scientific community is that it represents a timely opportunity to build upon existing concepts of checkpoints to expand our understanding of the inner workings of the critical checkpoint machinery. The present understanding has provided ample appreciation that response to checkpoint activation is manifested through coordinated inhibition of cyclin-dependent kinase (CDK) complexes in G1, S and/or the G2 phase in order to arrest the cell cycle. Kinase inhibition can occur through several mechanisms, including inhibitory phosphorylation of CDK, destruction of the cognate cyclins, and recruitment of CDK inhibitors from the INK and WAF1/CIP1 families. However, the wealth of information from recent discoveries needs to be examined critically to consolidate our conceptual knowledge of checkpoints. At the same time, there is acute awareness in the diversity of checkpoint response between cytotoxic agents, and this serves as a reminder of the magnitude of complexity that is inherent in checkpoint regulation. This volume is intended to bring the cancer research community closer toward an improved understanding of this regulation, how checkpoint abnormalities can impact negatively on cancer therapy, and emerging strategies to target checkpoint response as a therapeutic end-point.
Checkpoint Responses In Cancer Therapy
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Author : Wei Dai
language : en
Publisher: Springer Science & Business Media
Release Date : 2008-05-01
Checkpoint Responses In Cancer Therapy written by Wei Dai and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-05-01 with Medical categories.
Extensive research has uncovered a set of molecular surveillance mechanisms – commonly called “checkpoints” – which tightly monitor cell-cycle processes. Today’s anticancer drug development has identified many of these cell-cycle checkpoint molecules as effective targets. Research now promises to uncover a new generation of anticancer drugs with improved therapeutic indices based on their ability to target emerging checkpoint components. Checkpoint Responses in Cancer Therapy summarizes the advances made over the past 20 years, identifying components of cell-cycle checkpoints and their molecular regulation during checkpoint activation and validating the use of checkpoint proteins as targets for the development of anticancer drugs. This book’s distinguished panel of authors takes a close look at topics ranging from the major molecular players affecting DNA synthesis and the response to DNA damage to advances made in the identification of chemical compounds capable of inhibiting individual mitotic kinases. Illuminating and authoritative, Checkpoint Responses in Cancer Therapy offers a critical summary of findings for researchers in the pharmaceutical and biotechnology industries and a valuable resource for academic scientists in cancer research and the study of cell-cycle regulation, signal transduction and apoptosis.
Checkpoint Controls And Cancer
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Author : Axel H. Schönthal
language : en
Publisher: Springer Science & Business Media
Release Date : 2008-02-03
Checkpoint Controls And Cancer written by Axel H. Schönthal and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-02-03 with Medical categories.
Intracellular checkpoint controls constitute a network of signal transd- tion pathways that protect cells from external stresses and internal errors. Ext- nal stresses can be generated by the continuous assault of DNA-damaging agents, such as environmental mutagens, ultraviolet (UV) light, ionizing radiation, or the reactive oxygen species that can arise during normal cellular metabolism. In response to any of these assaults on the integrity of the genome, the activation of the network of checkpoint control pathways can lead to diverse cellular responses, such as cell cycle arrest, DNA repair, or elimination of the cell by cell death (apoptosis) if the damage cannot be repaired. Moreover, internal errors can occur during the highly orchestrated replication of the cellular genome and its distribution into daughter cells. Here, the temporal order of these cell cycle events must be strictly enforced—for example, to ensure that DNA replication is c- plete and occurs only once before cell division, or to monitor mitotic spindle assembly, and to prevent exit from mitosis until chromosome segregation has been completed. Thus, well functioning checkpoint mechanisms are central to the maintenance of genomic integrity and the basic viability of cells and, the- fore, are essential for proper development and survival. The importance of proper functioning of checkpoints becomes plainly obvious under conditions in which this control network malfunctions and fails. Depending on the severity and timing, failure of this machinery can lead to embryonic lethality, genetic diseases, and cancer.
Checkpoint Controls And Cancer
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Author : Axel H. Schönthal
language : en
Publisher: Springer Science & Business Media
Release Date : 2008-02-05
Checkpoint Controls And Cancer written by Axel H. Schönthal and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-02-05 with Medical categories.
Intracellular checkpoint controls constitute a network of signal transd- tion pathways that protect cells from external stresses and internal errors. Ext- nal stresses can be generated by the continuous assault of DNA-damaging agents, such as environmental mutagens, ultraviolet (UV) light, ionizing radiation, or the reactive oxygen species that can arise during normal cellular metabolism. In response to any of these assaults on the integrity of the genome, the activation of the network of checkpoint control pathways can lead to diverse cellular responses, such as cell cycle arrest, DNA repair, or elimination of the cell by cell death (apoptosis) if the damage cannot be repaired. Moreover, internal errors can occur during the highly orchestrated replication of the cellular genome and its distribution into daughter cells. Here, the temporal order of these cell cycle events must be strictly enforced—for example, to ensure that DNA replication is c- plete and occurs only once before cell division, or to monitor mitotic spindle assembly, and to prevent exit from mitosis until chromosome segregation has been completed. Thus, well functioning checkpoint mechanisms are central to the maintenance of genomic integrity and the basic viability of cells and, the- fore, are essential for proper development and survival. The importance of proper functioning of checkpoints becomes plainly obvious under conditions in which this control network malfunctions and fails. Depending on the severity and timing, failure of this machinery can lead to embryonic lethality, genetic diseases, and cancer.
Regulation Of Cancer Immune Checkpoints
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Author : Jie Xu
language : en
Publisher: Springer Nature
Release Date : 2020-03-17
Regulation Of Cancer Immune Checkpoints written by Jie Xu and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-03-17 with Medical categories.
This book systematically reviews the most important findings on cancer immune checkpoints, sharing essential insights into this rapidly evolving yet largely unexplored research topic. The past decade has seen major advances in cancer immune checkpoint therapy, which has demonstrated impressive clinical benefits. The family of checkpoints for mediating cancer immune evasion now includes CTLA-4, PD-1/PD-L1, CD27/CD70, FGL-1/LAG-3, Siglec-15, VISTA (PD-1L)/VSIG3, CD47/SIRPA, APOE/LILRB4, TIGIT, and many others. Despite these strides, most patients do not show lasting remission, and some cancers have been completely resistant to the therapy. The potentially lethal adverse effects of checkpoint blockade represent another major challenge, the mechanisms of which remain poorly understood. Compared to the cancer signaling pathways, such as p53 and Ras, mechanistic studies on immune checkpoint pathways are still in their infancy. To improve the responses to checkpoint blockade therapy and limit the adverse effects, it is essential to understand the molecular regulation of checkpoint molecules in both malignant and healthy cells/tissues. This book begins with an introduction to immune checkpoint therapy and its challenges, and subsequently describes the regulation of checkpoints at different levels. In closing, it discusses recent therapeutic developments based on mechanistic findings, and outlines goals for future translational studies. The book offers a valuable resource for researchers in the cancer immunotherapy field, helping to form a roadmap for checkpoint regulation and develop safer and more effective immunotherapies.
Checkpoint Controls And Cancer
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Author : Axel H. Schönthal
language : en
Publisher:
Release Date : 2004
Checkpoint Controls And Cancer written by Axel H. Schönthal and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2004 with categories.
Checkpoint Controls And Cancer
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Author : Axel H. Schönthal
language : en
Publisher:
Release Date : 2004
Checkpoint Controls And Cancer written by Axel H. Schönthal and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2004 with categories.
Signaling Pathways In Cancer Pathogenesis And Therapy
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Author : David A. Frank
language : en
Publisher: Springer Science & Business Media
Release Date : 2011-11-12
Signaling Pathways In Cancer Pathogenesis And Therapy written by David A. Frank and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-11-12 with Medical categories.
In recent years, increasing evidence has suggested that abnormal activation of signaling pathways is a critical event in cancer pathogenesis. In particular, activation of these pathways can lead to inappropriate cellular survival, proliferation, pluripotency, invasion, metastasis, and angiogenesis. Thus, understanding the mechanisms by which signaling pathways become subverted in a cancer cell can provide insight into critical events in cancer pathogenesis. Furthermore, as our ability to target specific molecular interactions advances, we now have the ability to design small molecules, protein therapeutics, and other forms of targeted therapies. By focusing on the specific molecular abnormalities in a cancer cell, these agents hold the potential to be much more effective and much less toxic than current cytotoxic therapies.
Cell Cycle Deregulation In Cancer
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Author : Greg H. Enders
language : en
Publisher: Springer Science & Business Media
Release Date : 2010-03-10
Cell Cycle Deregulation In Cancer written by Greg H. Enders and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010-03-10 with Medical categories.
Cancer is fundamentally a disease of abnormal cell proliferation: Cancer cells multiply when and where they should not. This proliferation entails escape from normal bounds imposed by the tissue environment, the internal biology of the cell (DNA damage, chromosomal imbalances, disorganized mitotic spindles), and the proliferative history of the cell (normal generational times). Some of the key oncogenic events in cancer directly perturb proteins that regulate progression through the cell division cycle, others alter cell cycle progression indirectly, through effects on signaling pathway that impinge on the cell cycle. This biology is fundamentally important in cancer therapy. Many of the workhorse treatments for cancer rely on killing proliferating cells. Furthermore, there is growing recognition that stem cell-transit amplifying cell hierarchies may persist or be generated during tumorigenesis, generating important functional heterogeneity in cell cycle control among tumor cells, with far-reaching scientific and clinical implications. This volume outlines major cell cycle perturbations that drive tumorigenesis and considers the prospects for using such knowledge in cancer therapy.
Molecular Biology Of The Cell
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Author : Bruce Alberts
language : en
Publisher:
Release Date : 2002
Molecular Biology Of The Cell written by Bruce Alberts and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2002 with Cytology categories.