Download or read book Cancer Therapeutics Targeting DNA Repair Pathways written by Amila Suraweera and published by Frontiers Media SA. This book was released on 2022-03-10 with total page 134 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book DNA Repair in Cancer Therapy written by Mark R. Kelley and published by Academic Press. This book was released on 2016-06-07 with total page 466 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA Repair and Cancer Therapy: Molecular Targets and Clinical Applications, Second Edition provides a comprehensive and timely reference that 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. Experts on DNA repair proteins from all areas of cancer biology research take readers from bench research to new therapeutic approaches. This book provides a detailed discussion of combination therapies, in other words, how the inhibition of repair pathways can be coupled with chemotherapy, radiation, or DNA damaging drugs. Newer areas in this edition include the role of DNA repair in chemotherapy induced peripheral neuropathy, radiation DNA damage, Fanconi anemia cross-link repair, translesion DNA polymerases, BRCA1-BRCA2 pathway for HR and synthetic lethality, and mechanisms of resistance to clinical PARP inhibitors. - Provides a comprehensive overview of the basic and translational research in DNA repair as a cancer therapeutic target - Includes timely updates from the earlier edition, including Fanconi Anemia cross-link repair, translesion DNA polymerases, chemotherapy induced peripheral neuropathy, and many other new areas within DNA repair and cancer therapy - Saves academic, medical, and pharma researchers time by allowing them to quickly access the very latest details on DNA repair and cancer therapy - Assists researchers and research clinicians in understanding the importance of the breakthroughs that are contributing to advances in disease-specific research

Download or read book Targeting the DNA Damage Response for Cancer Therapy written by Timothy A. Yap and published by Springer Nature. This book was released on 2023-12-19 with total page 333 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book discusses the latest developments in Poly (ADP-ribose) polymerase (PARP) inhibitor drug development. It focuses on the translational and clinical development of the latest drugs, as well as the evidence for regulatory approval of PARP inhibitors in multiple different molecular subtypes and tumor indications. The most-up-to-date information on basic scientific research on DNA repair pathways and the DNA Damage Response (DDR) is also covered. Every chapter contains insight into the preclinical, translational along with clinical aspects of a specific DDR inhibitor with key and expert opinion points reinforcing the most important concepts detailed to enable the reader to develop a deep understanding of the topic. Targeting the DNA Damage Response for Cancer Therapy comprehensively reviews the application of PARP and other DDR inhibitors across oncology disciplines. Therefore, it is a valuable resource for all medical professionals and researchers who use or who are researching the use of these inhibitors on a day-to-day basis.

Download or read book Targeting the DNA Damage Response for Anti Cancer Therapy written by John Pollard and published by Springer. This book was released on 2018-05-26 with total page 402 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.

Download or read book Cancer Associated Defects in the DNA Damage Response Drivers for Malignant Transformation and Potential Therapeutic Targets written by Marcel van Vugt and published by Frontiers Media SA. This book was released on 2016-10-17 with total page 111 pages. Available in PDF, EPUB and Kindle. Book excerpt: For this eBook, and the associated Research Topic in Frontiers in Genetics, entitled: ‘Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets’ we have selected 10 papers that each discusses important, yet distinct aspects of the response to DNA damage in normal cells and cancer cells. Using an evolutionary conserved signaling network called the ‘DNA damage response (DDR)’ cells maintain the integrity of their genome, and thus safeguard cellular functioning and the ability to create viably progeny. Initially, the DDR appeared to consist of few linear kinase-driven pathways. However, research over the past decades in model organisms, as well as in the human system has revealed that the DDR is a complex signaling network, wired by multiple parallel pathways and displaying extensive crosstalk. Besides phosphorylation, multiple other post-translational modifications, including ubiquitination and sumoylation, are involved to achieve chromatin remodeling and initiation of DNA repair. Also, rather than being a cell-intrinsic phenomenon, we increasingly appreciate that cell-cell communication is involved. The recognition and repair of DNA damage is essential to maintain normal physiology. Multiple pathological conditions have been attributed to defective DNA repair, most notably accelerated aging, neurodegeneration and cancer. In the context of cancer, through repair of DNA damage or elimination of irreparably damaged cells, the DDR clearly has a tumor-suppressive role. Indeed, many tumor cells show partially inactivated DDR signaling, which allows proliferation in the context of DNA damage-inducing oncogenes. Simultaneously, loss of specific DDR signaling nodes creates a specific dependence of tumor cells on their remaining DDR components, and thus creates therapeutic opportunities. Especially in the context of cancer treatment, numerous targeted agents are under investigation, either to potentiate the cytotoxic effects of chemo-radiotherapy, or to induce synthetic lethality with cancer-specific alterations, with the treatment of BRCA1/2 mutant cancers with PARP1 inhibitors as a prototype example. We have selected four review articles that provide insight into the key components and the wiring of the DDR and DNA repair. Torgovnick and Schumacher review the involvement of DNA repair in the initiation and treatment of cancer, Brinkmann et al., describe the involvement of ubiquitination in DNA damage signaling and Jaiswal and Lindqvist discuss how cell-extrinsic signaling participates in communication of DNA damage to neighboring cells. In addition, Shatneyeva and colleagues review the connection between the cellular response to DNA damage and escape from immune surveillance. Concerning the therapeutic application of targeting the DDR and DNA repair, three articles were included. Krajewska and van Vugt review the wiring of homologous recombination and how this offers therapeutic opportunities. Additionally, Knittel and colleagues describe how genetic loss of the central DDR component ATM in chronic lymphocytic leukemia can be exploited therapeutically by targeting certain parallel DNA repair pathways. Syljuasen and colleagues report on how targeting of the DDR can be used as a therapeutic strategy in lung cancer. Finally, three chapters describe newly identified regulators of the cellular response to DNA damage. Von Morgen et al. describe the R2TP complex, Lezzi and Fanciluuli review the involvement of Che-1/AATF in the DDR, and Ohms and co-authors describe how retrotransposons are at the basis of increased genomic instability. Altogether, these articles describe how defective responses to DNA damage underlie disease - and especially in the context of cancer -can be exploited to better treat disease.

Download or read book DNA Repair and Cancer written by Srinivasan Madhusudan and published by CRC Press. This book was released on 2013-01-22 with total page 714 pages. Available in PDF, EPUB and Kindle. Book excerpt: DNA repair is a rapidly advancing field in biology and these systems represent a major defense mechanism against environmental and intracellular damaging agents such as sunlight, ionizing radiation, and reactive oxygen species. With contributions from eminent researchers, this book explores the basics and current trends in this critical field. Topi

Download or read book DNA Repair of Cancer Stem Cells written by Lesley A Mathews and published by Springer Science & Business Media. This book was released on 2012-07-26 with total page 180 pages. Available in PDF, EPUB and Kindle. Book excerpt: The existence of ‘cancer stem cells’ (CSCs) has been a topic of heated debate for the last few years within the field of cancer biology. Their continuous characterization in a variety of solid tumors has lead to an abundance of evidence supporting their existence. CSCs are believed to be responsible for resistance against conventional treatment regimes of chemotherapy and radiation, ultimately, leading to metastasis and patient demise. To help aid clinicians, pharmaceutical companies and academic labs investigating how to better kill these highly aggressive cells we have summarized the DNA repair mechanism(s) and their role in the maintenance and regulation of both normal and cancer stem cells. Our book represents a comprehensive investigation into the highly effective DNA repair mechanisms of CSCs and what we need to understand in order to develop more advanced therapies to eradicate them from patients. Currently, there are no other published works entirely on DNA repair and Cancer Stem Cells. In addition, our book provides a comprehensive overview of CSC isolation and characterization from a variety of solid tumor types.

Download or read book Advances in DNA Repair in Cancer Therapy written by Lawrence Panasci and published by Springer Science & Business Media. This book was released on 2012-12-09 with total page 317 pages. Available in PDF, EPUB and Kindle. Book excerpt: ​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.​

Download or read book Cell Death written by Csaba Szabo and published by CRC Press. This book was released on 2000-06-22 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: Poly (ADP-ribose) polymerase (PARP), also termed poly (ADP-ribose) synthetase (PARS) is a nuclear enzyme with a wide range of functions, including regulation of DNA repair, cell differentiation, and gene expression. More than a decade after the identification of PARP-like enzymatic activities in mammalian cells, a novel role was proposed for this e

Download or read book System Biology Analysis of the Role of DNA Repair in Cancer Treatment Outcome written by Mengdi Qian and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is one of the most lethal and hard to cure diseases. The common treatments for cancer include surgery, radiation therapy, chemotherapy, immunotherapy and hormone therapy. Ionizing radiation (IR) is one of the main clinical treatments for cancer and it works by inducing DNA double strand breaks (DSBs), which are the most toxic DNA lesions that lead to cell death. The effectiveness of IR treatment depends on the amount of induced damage and the DNA damage repair status of the cancer cells. DSBs are repaired by multiple DNA repair pathways and this repair reduces the effectiveness of the treatment leading to resistance to IR. It has been shown in the literature that by targeting the DNA repair pathways the treatment efficacy can be modulated.In this work, a systems biology approach is used to quantitatively study the role of DNA repair pathways in determining and improving the radiation treatment outcome. Specifically, the mathematical models of DNA repair pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are developed for analyzing the role of DNA repair in enhancing the treatment sensitivity for prostate cancer (PCa) when a combination of radiation and hormone deprivation therapies is used. DSBs are repaired by one of the two DNA repair pathways: NHEJ and homologous recombination (HR). NHEJ is the major pathway, whereas HR is restricted to S- or G2-phases of the cell cycle after DNA replication has been completed. The cell cycle specific contribution of the repair pathways are incorporated into the computational models. A comprehensive identifiability analysis is carried out to determine the factors affecting parameter identifiability and strategies to increase identifiability are developed. In parallel to the NHEJ and HR models, a computational model of the base excision repair (BER) pathway is developed to analyze its role in response to chemotherapy under different treatment scenarios.Combination treatment strategies that aim to inhibit the functional DNA repair pathways for the cancer cells that are defective in other repair pathways achieve synthetic lethality. One such strategy is the use of PARP inhibitors (PARPi) in addition to the combination treatment with IR and ADT. The experimental data in the literature show that AR promotes both NHEJ and HR following IR, and inhibition of AR by ADT impairs both of these pathways in PCa cells leading to either increased radiosensitivity or sensitization to PARP inhibitors. The effect of using PARPi in this scenario has been computationally analyzed in this work by extending the modeling efforts to include the effect of PARP inhibitors on the treatment outcome. The inhibition of BER by PARPi is also quantitatively studied. The models and findings in this work can then be extended to other cancers, such as lung cancer and ovarian cancer that benefit from similar synthetic lethality.

Download or read book New Research Directions in DNA Repair written by Clark Chen and published by BoD – Books on Demand. This book was released on 2013-05-22 with total page 676 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is intended for students and scientists working in the field of DNA repair. Select topics are presented here to illustrate novel concepts in DNA repair, the cross-talks between DNA repair and other fundamental cellular processes, and clinical translational efforts based on paradigms established in DNA repair. The book should serve as a supplementary text in courses and seminars as well as a general reference for biologists with an interest in DNA repair.

Download or read book Targeting DNA Repair Deficiencies with Small Molecule Drugs for Cancer Treatment written by Laura Sesma Sanz and published by . This book was released on 2021 with total page 251 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is a very heterogeneous disease with a multitude of different facets. However, even different types of cancer share a set of characteristics that can be exploited for therapeutic purposes. In our group we are interested in DNA damage and repair, particularly in the context of cancer, since genomic instability is considered one of the “Hallmarks of Cancer”. Homologous Recombination (HR) is a mechanism used by cells to repair Double-Strand Breaks, the most harmful type of DNA damage. Deficiencies in this pathway of DNA repair results in increased genomic instability and has been observed in a wide variety of tumours, notably in ovarian and breast cancer. The events most commonly associated with HR defects are genetic alterations in HR related genes such as BRCA1, BRCA2 and the more recently identified PALB2. The concept of synthetic lethality describes the incompatibility or lethality of two simultaneous events that are individually tolerable. Cancer research is taking advantage of this idea to develop new targeted treatments. The most important success of synthetic lethality-based therapy development is the case of PARP inhibitors. It was observed that inhibition of PARP-1, an abundant protein involved in many cellular processes, including DNA repair, is synthetically lethal with defects in Homologous Recombination. Therefore, PARP inhibitors were developed to specifically target HR-deficient tumours while sparing normal HR-proficient tissues. Nevertheless, as with most drugs, many patients develop resistance to PARP inhibitors, which can lead to disease recurrence, thus highlighting the need for alternative treatment options. Recent research has focused not only on finding new synthetic lethal interactions but also on developing new combinations of molecules to potentiate their effect and both prevent and counteract resistances to drugs. Following this idea, the main objective of my doctoral work was to find new potential treatments for HR-deficient tumours, alone or in combination with PARP inhibitors. Within this project, we also developed a new in cellulo screen system, based on analyzing the effects of the studied compounds on cell populations with different HR capacities. We stably transfected HR-proficient and deficient cell lines to express either red or green fluorescent proteins, respectively, and co-cultured them with more than 1000 drugs of a library of compounds. We identified CB1954, previously studied as a prodrug, to specifically target HR-deficient cells. Interestingly, CB1954 synergizes with PARP inhibitors in both HR-deficient and proficient cells, thus constituting a promising combination with interesting potential. Additionally, we identified synergy between PARP inhibition (Talazoparib) and type I PRMT inhibition (MS023) in MTAP-negative NSCLC and ovarian cancer cells, both PARPi sensitive and resistant. Both combinations need further examination to better characterize their mechanisms of action and identify the biomarkers for sensitivity and resistance to the treatments. We are currently studying the effects of CB1954+PARPi on cell fate and, since we have confirmed the effects of the drugs and the synergy in 3D cultured cells, we are testing the combination in ovarian cancer xenograft mouse models. In summary, we have developed a new fluorescence-based method to screen for compounds having a synthetic lethal effect, which could be adapted to the study of other pathologies. We have also identified and tested two new compound combinations that could potentially be applied to the treatment of tumours resistant to PARP inhibitors.

Download or read book The Role of DNA Repair Pathways in Resistance to Chemotherapy and Radiotherapy in Cancer written by José Díaz-Chávez and published by Frontiers Media SA. This book was released on 2022-04-29 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Exploiting DNA Damage Response in the Era of Precision Oncology written by Yitzhak Zimmer and published by Frontiers Media SA. This book was released on 2020-12-11 with total page 114 pages. Available in PDF, EPUB and Kindle. Book excerpt: Topic Editor Christian Reinhardt has received funding from companies Gilead, and lecture fees from Abbvie, Merck, and AstraZeneca. All other topic editors declare no competing interests with regards to the Research Topic subject.

Download or read book Dna Repair Genetic Instability And Cancer written by Qingyi Wei and published by World Scientific. This book was released on 2007-01-08 with total page 374 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume describes the elaborate surveillance systems and various DNA repair mechanisms that ensure accurate passage of genetic information onto daughter cells. In particular, it narrates how the cell cycle checkpoint and DNA repair machineries detect and restore DNA damages that are embedded in millions to billions of normal base pairs. The scope of the book ranges from biochemical analyses and structural details of DNA repair proteins, to integrative genomics and population-based studies. It provides a snapshot of current understanding about some of the major DNA repair pathways, including base-excision repair, nucleotide excision repair, mismatch repair, homologous recombination, and non-homologous end-joining as well as cell cycle checkpoints and translesion DNA synthesis. One of the particular emphases of the book is the link between inherited DNA repair deficiencies and susceptibility to cancer in the general population. For the first time, the book brings together a collection of review articles written by a group of active and laboratory-based investigators who have a clear understanding of the recent advances in the fields of DNA damage repair and genomic stability and their implications in carcinogenesis, new approaches in cancer therapy, and cancer prevention.

Download or read book Cancer associated Defects in the DNA Damage Response Drivers for Malignant Transformation and Potential Therapeutic Targets written by and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: For this eBook, and the associated Research Topic in Frontiers in Genetics, entitled: 'Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets' we have selected 10 papers that each discusses important, yet distinct aspects of the response to DNA damage in normal cells and cancer cells. Using an evolutionary conserved signaling network called the 'DNA damage response (DDR)' cells maintain the integrity of their genome, and thus safeguard cellular functioning and the ability to create viably progeny. Initially, the DDR appeared to consist of few linear kinase-driven pathways. However, research over the past decades in model organisms, as well as in the human system has revealed that the DDR is a complex signaling network, wired by multiple parallel pathways and displaying extensive crosstalk. Besides phosphorylation, multiple other post-translational modifications, including ubiquitination and sumoylation, are involved to achieve chromatin remodeling and initiation of DNA repair. Also, rather than being a cell-intrinsic phenomenon, we increasingly appreciate that cell-cell communication is involved. The recognition and repair of DNA damage is essential to maintain normal physiology. Multiple pathological conditions have been attributed to defective DNA repair, most notably accelerated aging, neurodegeneration and cancer. In the context of cancer, through repair of DNA damage or elimination of irreparably damaged cells, the DDR clearly has a tumor-suppressive role. Indeed, many tumor cells show partially inactivated DDR signaling, which allows proliferation in the context of DNA damage-inducing oncogenes. Simultaneously, loss of specific DDR signaling nodes creates a specific dependence of tumor cells on their remaining DDR components, and thus creates therapeutic opportunities. Especially in the context of cancer treatment, numerous targeted agents are under investigation, either to potentiate the cytotoxic effects of chemo-radiotherapy, or to induce synthetic lethality with cancer-specific alterations, with the treatment of BRCA1/2 mutant cancers with PARP1 inhibitors as a prototype example. We have selected four review articles that provide insight into the key components and the wiring of the DDR and DNA repair. Torgovnick and Schumacher review the involvement of DNA repair in the initiation and treatment of cancer, Brinkmann et al., describe the involvement of ubiquitination in DNA damage signaling and Jaiswal and Lindqvist discuss how cell-extrinsic signaling participates in communication of DNA damage to neighboring cells. In addition, Shatneyeva and colleagues review the connection between the cellular response to DNA damage and escape from immune surveillance. Concerning the therapeutic application of targeting the DDR and DNA repair, three articles were included. Krajewska and van Vugt review the wiring of homologous recombination and how this offers therapeutic opportunities. Additionally, Knittel and colleagues describe how genetic loss of the central DDR component ATM in chronic lymphocytic leukemia can be exploited therapeutically by targeting certain parallel DNA repair pathways. Syljuasen and colleagues report on how targeting of the DDR can be used as a therapeutic strategy in lung cancer. Finally, three chapters describe newly identified regulators of the cellular response to DNA damage. Von Morgen et al. describe the R2TP complex, Lezzi and Fanciluuli review the involvement of Che-1/AATF in the DDR, and Ohms and co-authors describe how retrotransposons are at the basis of increased genomic instability. Altogether, these articles describe how defective responses to DNA damage underlie disease - and especially in the context of cancer -can be exploited to better treat disease.

Download or read book Stress Response Pathways in Cancer written by Georg T. Wondrak and published by Springer. This book was released on 2014-11-07 with total page 450 pages. Available in PDF, EPUB and Kindle. Book excerpt: It is now established that dysregulated cell stress response pathways play a critical role in tumorigenesis, and a refined mechanistic understanding of this phenomenon at the molecular level promises to open new avenues for targeted therapeutic strategies that may benefit cancer patients in the near future. Coauthored by recognized leaders in cancer research from five continents, this novel book provides a comprehensive perspective on cell stress response pathways and therapeutic opportunities. Focusing on the role of genotoxic, proteotoxic, oxidative, metabolic, and inflammatory stress in tumorigenesis, the book is essential reading for students, basic researchers, and biomedical health care professionals interested in cancer and therapeutic development.