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The Role Of Dna Repair Pathways In Resistance To Chemotherapy And Radiotherapy In Cancer
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Book Synopsis The Role of DNA Repair Pathways in Resistance to Chemotherapy and Radiotherapy in Cancer by : José Díaz-Chávez
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:
Book Synopsis System Biology Analysis of the Role of DNA Repair in Cancer Treatment Outcome by : Mengdi Qian
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.
Book Synopsis DNA Repair and Cancer by : Srinivasan Madhusudan
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
Book Synopsis DNA Repair in Cancer Therapy by : Mark R. Kelley
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
Book Synopsis DNA Repair of Cancer Stem Cells by : Lesley A Mathews
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.
Book Synopsis DNA Repair in Cancer Therapy by : Lawrence C. Panasci
Download or read book DNA Repair in Cancer Therapy written by Lawrence C. Panasci and published by Springer Science & Business Media. This book was released on 2004-03-19 with total page 547 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Book Synopsis Advances in DNA Repair in Cancer Therapy by : Lawrence Panasci
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.
Book Synopsis Cancer-Associated Defects in the DNA Damage Response: Drivers for Malignant Transformation and Potential Therapeutic Targets by : Marcel van Vugt
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.
Book Synopsis Molecular Determinants of Radiation Response by : Theodore L. DeWeese
Download or read book Molecular Determinants of Radiation Response written by Theodore L. DeWeese and published by Springer Science & Business Media. This book was released on 2011-03-23 with total page 282 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Determinants of Radiation Response includes chapters by expert authors who detail the present understanding of key DNA damage response pathways and proteins. The chapters include comprehensive discussions on where and how specific alterations in function of these pathways and proteins result in substantive modifications of cellular response to DNA injury. Given the importance of therapies that induce DNA injury in the management of human disease, this book is timely and relevant for basic and translational researchers, as well as clinicians alike.
Book Synopsis Targeting the DNA Damage Response for Anti-Cancer Therapy by : John Pollard
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.
Book Synopsis New Research Directions in DNA Repair by : Clark Chen
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.
Book Synopsis Targeting the DNA Damage Response for Cancer Therapy by : Timothy A. Yap
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.
Book Synopsis Exploiting DNA Damage Response in the Era of Precision Oncology by : Yitzhak Zimmer
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.
Book Synopsis Pharmacogenetics of the DNA Repair and Oxidative Stress Pathways in Outcomes of Cancer Patients by : Nataliya Kuptsova
Download or read book Pharmacogenetics of the DNA Repair and Oxidative Stress Pathways in Outcomes of Cancer Patients written by Nataliya Kuptsova and published by . This book was released on 2008 with total page 175 pages. Available in PDF, EPUB and Kindle. Book excerpt: Introduction: Radiation and chemotherapy, widely used for treatment of neoplasms, cause a variety of DNA damage lesions to the genome. Generation of free radicals and reactive oxygen species (ROS), as well as induction of single- and double-strand DNA breaks, are common mechanisms of action of radiotherapy and chemotherapeutic agents. Overexpression of enzymes participating in detoxification of xenobiotics and enhanced activity of DNA repair pathways are some of the established causes of resistance to treatment. Inherited genetic variation, common throughout the genome, largely contributes to modified effects of anti-cancer treatment through altered activity, encoded by polymorphic genes. In this dissertation, we investigated relationships between treatment outcomes and polymorphisms in 1) glutathione-S-transferases (GST) and other oxidative stress-related enzymes, and 2) base-, nucleotide-excision, and double-strand break repair pathways.^Patients and Methods: Early stage breast cancer patients from a German cohort were genotyped for polymorphisms in genes related to oxidative stress, GSTA1, GSTM1, GSTT1, GSTP1, CAT, MnSOD, eNOS, and MPO, in relation to late dermatologic side effects of radiation treatment. Acute myeloid leukemia (AML) adult patients from two study populations (Southwest Oncology Group (SWOG) and Roswell Park Cancer Institute (RPCI)) were genotyped for APE1, ERCC1, ERCC2/(XPD), XRCC1, XRCC3 and XRCC1, ERCC2/(XPD) polymorphisms respectively. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was used in genotyping of all patients. Logistic and proportional hazards regression models were applied to evaluate relationships between genotypes/haplotypes and toxicities, response to treatment and overall survival.^Results: Among women treated with breast-conserving surgery and radiation, patients with variant GSTA1 genotypes were at significantly increased risk of telangiectasia (OR 1.86, 95% CI 1.11-3.11). Conversely, reduced odds of telangiectasia was noted for lower-activity eNOS genotypes (OR 0.58, 95% CI 0.36-0.93). Furthermore, genotype effects were modified by follow-up time. In the AML SWOG cohort, patients with XPD Gln751C/Asp312G (`D') haplotype were more likely to have complete response (CR) [OR=3.06 (95% CI: 1.44-6.70)] and less likely to have resistant disease (RD) [OR=0.32 (95%CI: 0.14-0.72)] than patients with other haplotypes. ERCC1 polymorphisms were significantly associated with lung (P=.037) and metabolic (P=.041) toxicities, and patients with the XRCC3 241Met variant had reduced risk of liver toxicity (OR=0.32, 95%CI: 0.11-0.95). Significant associations with other toxicities were also found for variant XPD genotypes/haplotypes.^Among RPCI AML patients, differential chemotherapy responses were observed in patients with variant XPD 312, XPD 751 and XPD haplotypes. Effects were modified by AML onset. Among secondary AML patients, XPD 751Gln/Gln variant was associated with 7.07-higher odds of achieving complete remission (CR), (95% CI, 1.42-35.18); XPD 312Asn/Asn genotype was associated with 11.23-fold increase in CR, (95% CI, 2.23-56.63). Patients in `BB/DA' (751Gln/312Asn-751Gln/312Asn/751Gln/Asp312-Lys751-Asp312) variant diplotype category were more likely to achieve CR (OR=31.10 (95% CI: 3.98-242.88)). Significant associations between better overall survival (OS) and XPD variant genotypes/haplotypes were also observed. Furthermore, variant XPD genotypes/haplotypes were associated with significantly reduced risk of nausea/vomiting; in `BB/DA' diplotype group this risk was (OR 0.35, 95% CI, 0.13-0.90).^Significant relationships between infectious complications after induction chemotherapy and heterozygote XPD genotypes/haplotypes were seen. Conclusions: The findings from this research indicate significant associations between inter-individual genetic variations in oxidative stress and DNA repair enzymes and response to treatment, overall survival, as well as development of radiation- and chemotherapy-induced toxicities. With validation of results in larger samples, these findings could lead to optimizing individual radio- and chemotherapy options for patients with cancer.
Book Synopsis Molecular Biology of Prostate Cancer by : Manfred Wirth
Download or read book Molecular Biology of Prostate Cancer written by Manfred Wirth and published by Walter de Gruyter. This book was released on 2013-05-22 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis DNA Damage and Repair by : Jac A. Nickoloff
Download or read book DNA Damage and Repair written by Jac A. Nickoloff and published by Springer Science & Business Media. This book was released on 1998-08-12 with total page 1050 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cutting edge reviews by leading researchers illuminate key aspects of DNA repair in mammalian systems and its relationship to human genetic disease and cancer. Major topics include UV and X-Ray repair, repair of chemical damage, recombinational repair, mismatch repair, transcription-repair coupling, and the role of DNA repair in disease prevention. Extensive up-to-date references and rigorous peer-review of each chapter make this volume definitive and bring it to the active frontiers of research.
Book Synopsis Cancer Therapeutics: Targeting DNA Repair Pathways by : Amila Suraweera
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:
