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  1. Book: Targeting the DNA Damage Response for Cancer Therapy

    Shapiro, Geoffrey I. / Yap, Timothy A.

    (Cancer Treatment and Research)

    2023  

    Author's details Dr. Timothy A. Yap is a Medical Oncology Physician-Scientist and tenured Professor based at the University of Texas MD Anderson Cancer Center. He is a Professor in the Department for Investigational Cancer Therapeutics (Phase I Program), and the Department of Thoracic/Head and Neck Medical Oncology. § Dr. Yap is Vice President and Head of Clinical Development in the Therapeutics Discovery Division, a drug discovery biopharmaceutical division where drug discovery and clinical translation are seamlessly integrated. §He is also the Associate Director of Translational Research in the Institute for Personalized Cancer Therapy, which is an integrated research and clinical trials program aimed at implementing personalized cancer therapy and improving patient outcomes. § Dr. Yap's main research focuses on the first-in-human and combinatorial development of molecularly targeted agents and immunotherapies, and their acceleration through clinical studies using novel predictive and pharmacod
    Series title Cancer Treatment and Research
    Keywords DNArepairpathways ; PARPtrapping ; inhibition ; ResistanceMechanisms ; homologousrecombination ; Castration-resistantprostatecancer ; Radiosensitization ; Poly(ADP-ribose)polymerase ; BRCAmutantcancers ; DNA repair pathways ; PARP trapping ; Inhibition ; Resistance mechanisms ; Homologous recombination ; Castration-resistant prostate cancer ; Poly (ADP-ribose) polymerase ; BRCA mutant cancers
    Language English
    Size 340 p.
    Edition 1
    Publisher Springer International Publishing
    Document type Book
    Note PDA Manuell_24
    Format 160 x 241 x 23
    ISBN 9783031300646 ; 3031300645
    Database PDA

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  2. Book: Phase I Oncology Drug Development

    Yap, Timothy A. / Rodon, Jordi / Hong, David S.

    2020  

    Abstract: This book provides a detailed review of how oncology drug development has changed over the past decade, and serves as a comprehensive guide for the practicalities in setting up phase I trials. The book covers strategies to accelerate the development of ... ...

    Author's details Dr Timothy A. Yap MBBS PhD FRCP: Dr Timothy Yap is a Medical Oncologist and Physician-Scientist based at the University of Texas MD Anderson Cancer Center. He is an Associate Professor in the Department for Investigational Cancer Therapeutics (Phase I Program), and the Department of Thoracic/Head and Neck Medical Oncology. Dr Yap is the Medical Director of the Institute for Applied Cancer Science, a drug discovery biopharmaceutical unit where drug discovery and clinical translation are seamlessly integrated. He is also the Associate Director of Translational Research in the Institute for Personalized Cancer Therapy, which is an integrated research and clinical trials program aimed at implementing personalized cancer therapy and improving patient outcomes. Prior to his current position, Dr Yap was a Clinician Scientist at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden Hospital in London, United Kingdom.§§Dr Yap gained his BSc degree w
    Abstract This book provides a detailed review of how oncology drug development has changed over the past decade, and serves as a comprehensive guide for the practicalities in setting up phase I trials. The book covers strategies to accelerate the development of novel antitumor compounds from the laboratory to clinical trials and beyond through the use of innovative mechanism-of-action pharmacodynamic biomarkers and pharmacokinetic studies. -- -- The reader will learn about all aspects of modern phase...
    Keywords MHMC020 ; MHMOI60 ; MHMOI10 ; drug development ; precision medicine ; immunotherapy ; targeted therapy ; chemotherapy ; oncology ; targeted agents ; radiotherapy ; early phase clinical trials ; biomarkers ; Radiaton Oncology
    Language English
    Size 352 p.
    Edition 1
    Publisher Springer International Publishing
    Document type Book
    Note PDA Manuell_7
    Format 155 x 235
    ISBN 9783030476816 ; 3030476812
    Database PDA

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  3. Book ; Online ; E-Book: Phase I oncology drug development

    Yap, Timothy A. / Hong, David S. / Rodon, Jordi

    2020  

    Abstract: This book provides a detailed review of how oncology drug development has changed over the past decade, and serves as a comprehensive guide for the practicalities in setting up phase I trials. The book covers strategies to accelerate the development of ... ...

    Author's details Timothy A. Yap, Jordi Rodon, David S. Hong, editors
    Abstract This book provides a detailed review of how oncology drug development has changed over the past decade, and serves as a comprehensive guide for the practicalities in setting up phase I trials. The book covers strategies to accelerate the development of novel antitumor compounds from the laboratory to clinical trials and beyond through the use of innovative mechanism-of-action pharmacodynamic biomarkers and pharmacokinetic studies. The reader will learn about all aspects of modern phase I trial designs, including the incorporation of precision medicine strategies, and approaches for rational patient allocation to novel anticancer therapies. Circulating biomarkers to assess mechanisms of response and resistance are changing the way we are assessing patient selection and are also covered in this book. The development of the different classes of antitumor agents are discussed, including chemotherapy, molecularly targeted agents, immunotherapies and also radiotherapy. The authors also discuss the lessons that the oncology field has learnt from the development of hematology-oncology drugs and how such strategies can be carried over into therapies for solid tumors. There is a dedicated chapter that covers the specialized statistical approaches necessary for phase I trial designs, including novel Bayesian strategies for dose escalation. This volume is designed to help clinicians better understand phase I clinical trials, but would also be of use to translational researchers (MDs and PhDs), and drug developers from academia and industry interested in cancer drug development. It could also be of use to phase I trial study coordinators, oncology nurses and advanced practice providers. Other health professionals interested in the treatment of cancer will also find this book of great value. .
    MeSH term(s) Antineoplastic Agents. ; Drug Development. ; Neoplasms/drug therapy. ; Clinical Trials, Phase I as Topic.
    Keywords Antineoplastic agents/Design ; Cancer/Chemotherapy ; Drug development
    Subject code 616.994061
    Language English
    Size 1 online resource (X, 352 pages, 47 illustration, 45 illustrations in color.)
    Edition 1st ed. 2020.
    Publisher Springer
    Publishing place Cham, Switzerland
    Document type Book ; Online ; E-Book
    Remark Zugriff für angemeldete ZB MED-Nutzerinnen und -Nutzer
    ISBN 3-030-47682-0 ; 3-030-47681-2 ; 978-3-030-47682-3 ; 978-3-030-47681-6
    DOI 10.1007/978-3-030-47682-3
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  4. Article ; Online: The Principles and Practice of PARP Inhibitor Therapy.

    Yap, Timothy A / Coleman, Robert L

    Cancer journal (Sudbury, Mass.)

    2021  Volume 27, Issue 6, Page(s) 430–431

    MeSH term(s) Cell Line, Tumor ; Humans ; Molecular Targeted Therapy ; Ovarian Neoplasms/drug therapy ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
    Chemical Substances Poly(ADP-ribose) Polymerase Inhibitors
    Language English
    Publishing date 2021-12-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2018400-1
    ISSN 1540-336X ; 1528-9117 ; 1081-4442
    ISSN (online) 1540-336X
    ISSN 1528-9117 ; 1081-4442
    DOI 10.1097/PPO.0000000000000563
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4470: Show issues Location:
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  5. Article ; Online: Aligning Germline Cancer Predisposition With Tumor-Based Next-Generation Sequencing for Modern Oncology Diagnosis, Interception, and Therapeutic Development.

    Yap, Timothy A / Stadler, Zsofia K / Stout, Leigh Anne / Schneider, Bryan P

    American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

    2023  Volume 43, Page(s) e390738

    Abstract: In the era of precision medicine, genomic interrogation for identification of both germline and somatic genetic alterations has become increasingly important. While such germline testing was usually undertaken via a phenotype-driven single-gene approach, ...

    Abstract In the era of precision medicine, genomic interrogation for identification of both germline and somatic genetic alterations has become increasingly important. While such germline testing was usually undertaken via a phenotype-driven single-gene approach, with the advent of next-generation sequencing (NGS) technologies, the widespread utilization of multigene panels, often agnostic of cancer phenotype, has become a commonplace in many different cancer types. At the same time, somatic tumor testing in oncology performed for the purpose of guiding therapeutic decisions for targeted therapies has also rapidly expanded, recently starting to incorporate not just patients with recurrent or metastatic cancer but even patients with early-stage disease. An integrated approach may be the best approach for the optimal management of patients with different cancers. The lack of complete congruence between germline and somatic NGS tests does not minimize the power or importance of either, but highlights the need to understand their limitations so as not to overlook an important finding or omission. NGS tests built to more uniformly and comprehensively evaluate both the germline and tumor simultaneously are urgently required and are in development. In this article, we discuss approaches to somatic and germline analyses in patients with cancer and the knowledge gained from integration of tumor-normal sequencing. We also detail strategies for the incorporation of genomic analysis into oncology care delivery models and the important emergence of poly(ADP-ribose) polymerase and other DNA Damage Response inhibitors in the clinic for patients with cancer with germline and somatic
    MeSH term(s) Humans ; Neoplasms/diagnosis ; Neoplasms/genetics ; Neoplasms/therapy ; Medical Oncology ; High-Throughput Nucleotide Sequencing ; Neoplasms, Second Primary ; Disease Susceptibility ; Germ Cells
    Language English
    Publishing date 2023-07-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2431126-1
    ISSN 1548-8756 ; 1548-8748
    ISSN (online) 1548-8756
    ISSN 1548-8748
    DOI 10.1200/EDBK_390738
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: PARP inhibitors: enhancing efficacy through rational combinations.

    Bhamidipati, Deepak / Haro-Silerio, Jaime I / Yap, Timothy A / Ngoi, Natalie

    British journal of cancer

    2023  Volume 129, Issue 6, Page(s) 904–916

    Abstract: Poly (ADP-ribose) polymerase inhibitors (PARPi) have significantly changed the treatment landscape for tumours harbouring defects in genes involved in homologous repair (HR) such as BRCA1 and BRCA2. Despite initial responsiveness to PARPi, tumours ... ...

    Abstract Poly (ADP-ribose) polymerase inhibitors (PARPi) have significantly changed the treatment landscape for tumours harbouring defects in genes involved in homologous repair (HR) such as BRCA1 and BRCA2. Despite initial responsiveness to PARPi, tumours eventually develop resistance through a variety of mechanisms. Rational combination strategies involving PARPi have been explored and are in various stages of clinical development. PARPi combinations have the potential to enhance efficacy through synergistic activity, and also potentially sensitise innately PARPi-resistant tumours to PARPi. Initial combinations involving PARPi with chemotherapy were hindered by significant overlapping haematologic toxicity, but newer combinations with fewer toxicities and more targeted approaches are undergoing evaluation. In this review, we discuss the mechanisms of PARPi resistance and review the rationale and clinical evidence for various PARPi combinations including combinations with chemotherapy, immunotherapy, and targeted therapies. We also highlight emerging PARPi combinations with promising preclinical evidence.
    MeSH term(s) Female ; Humans ; Genes, BRCA2 ; Neoplasms/drug therapy ; Neoplasms/genetics ; Ovarian Neoplasms/genetics ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
    Chemical Substances Poly(ADP-ribose) Polymerase Inhibitors
    Language English
    Publishing date 2023-07-10
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 80075-2
    ISSN 1532-1827 ; 0007-0920
    ISSN (online) 1532-1827
    ISSN 0007-0920
    DOI 10.1038/s41416-023-02326-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Targeting the DNA damage response beyond poly(ADP-ribose) polymerase inhibitors: novel agents and rational combinations.

    Ngoi, Natalie Y L / Westin, Shannon N / Yap, Timothy A

    Current opinion in oncology

    2022  Volume 34, Issue 5, Page(s) 559–569

    Abstract: Purpose of review: Poly(ADP-ribose) polymerase (PARP) inhibitors have transformed treatment paradigms in multiple cancer types defined by homologous recombination deficiency (HRD) and have become the archetypal example of synthetic lethal targeting ... ...

    Abstract Purpose of review: Poly(ADP-ribose) polymerase (PARP) inhibitors have transformed treatment paradigms in multiple cancer types defined by homologous recombination deficiency (HRD) and have become the archetypal example of synthetic lethal targeting within the DNA damage response (DDR). Despite this success, primary and acquired resistance to PARP inhibition inevitability threaten the efficacy and durability of response to these drugs. Beyond PARP inhibitors, recent advances in large-scale functional genomic screens have led to the identification of a steadily growing list of genetic dependencies across the DDR landscape. This has led to a wide array of novel synthetic lethal targets and corresponding inhibitors, which hold promise to widen the application of DDR inhibitors beyond HRD and potentially address PARP inhibitor resistance.
    Recent findings: In this review, we describe key synthetic lethal interactions that have been identified across the DDR landscape, summarize the early phase clinical development of the most promising DDR inhibitors, and highlight relevant combinations of DDR inhibitors with chemotherapy and other novel cancer therapies, which are anticipated to make an impact in rationally selected patient populations.
    Summary: The DDR landscape holds multiple opportunities for synthetic lethal targeting with multiple novel DDR inhibitors being evaluated on early phase clinical trials. Key challenges remain in optimizing the therapeutic window of ATR and WEE1 inhibitors as monotherapy and in combination approaches.
    MeSH term(s) Antineoplastic Agents/therapeutic use ; DNA Damage ; DNA Repair ; Humans ; Neoplasms/drug therapy ; Neoplasms/genetics ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use
    Chemical Substances Antineoplastic Agents ; Poly(ADP-ribose) Polymerase Inhibitors
    Language English
    Publishing date 2022-07-05
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1049384-0
    ISSN 1531-703X ; 1040-8746
    ISSN (online) 1531-703X
    ISSN 1040-8746
    DOI 10.1097/CCO.0000000000000867
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Global Implementation of Precision Oncology.

    Yam, Clinton / Ma, Brigette B Y / Yap, Timothy A

    JCO precision oncology

    2021  Volume 5

    MeSH term(s) Data Collection ; Humans ; Medical Oncology ; Neoplasms/diagnosis ; Precision Medicine
    Language English
    Publishing date 2021-05-18
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ISSN 2473-4284
    ISSN (online) 2473-4284
    DOI 10.1200/PO.21.00001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Precision Medicine in Oncology-Toward the Integrated Targeting of Somatic and Germline Genomic Aberrations.

    Yap, Timothy A / Johnson, Amber / Meric-Bernstam, Funda

    JAMA oncology

    2021  Volume 7, Issue 4, Page(s) 507–509

    MeSH term(s) Genomics ; Germ Cells ; Humans ; Medical Oncology ; Precision Medicine
    Language English
    Publishing date 2021-02-07
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ISSN 2374-2445
    ISSN (online) 2374-2445
    DOI 10.1001/jamaoncol.2020.7988
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  10. Article ; Online: Development of the PARP inhibitor talazoparib for the treatment of advanced

    Hobbs, Evthokia A / Litton, Jennifer K / Yap, Timothy A

    Expert opinion on pharmacotherapy

    2021  Volume 22, Issue 14, Page(s) 1825–1837

    Abstract: Introduction: BRCA1: Areas covered: In this review, the authors highlight the relevant clinical trials of talazoparib, as well as, safety, tolerability, and quality of life considerations. They also examine putative response and resistance mechanisms, ...

    Abstract Introduction: BRCA1
    Areas covered: In this review, the authors highlight the relevant clinical trials of talazoparib, as well as, safety, tolerability, and quality of life considerations. They also examine putative response and resistance mechanisms, and rational combinatorial therapeutic strategies under development.
    Expert opinion: Talazoparib has been a major advance in the treatment of germline
    MeSH term(s) BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Female ; Germ-Line Mutation ; Humans ; Phthalazines ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Quality of Life
    Chemical Substances BRCA1 Protein ; BRCA1 protein, human ; BRCA2 Protein ; BRCA2 protein, human ; Phthalazines ; Poly(ADP-ribose) Polymerase Inhibitors ; talazoparib (9QHX048FRV)
    Language English
    Publishing date 2021-07-26
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2001535-5
    ISSN 1744-7666 ; 1465-6566
    ISSN (online) 1744-7666
    ISSN 1465-6566
    DOI 10.1080/14656566.2021.1952181
    Database MEDical Literature Analysis and Retrieval System OnLINE

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