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PARP Inhibitors for Cancer Therapy (eBook)

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2015 | 2015
XIX, 591 Seiten
Springer International Publishing (Verlag)
978-3-319-14151-0 (ISBN)

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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.



Nicola Jane Curtin, Ph.D. is Professor of Experimental Cancer Therapeutics at Newcastle University. Dr. Curtin is also the team leader for DNA damage signalling and repair projects within CR-UK Drug Development Programme.

Ricky Sharma is Associate Professor at the University of Oxford and Honorary Consultant in Clinical Oncology at the Oxford University Hospitals NHS Trust. He graduated in medicine from the University of Cambridge, and subsequently trained in toxicology, general internal medicine, medical oncology and clinical oncology in Cambridge, Glasgow, Leicester and London. Since 2006, he has led a translational research group at the University of Oxford focussed on DNA damage repair and the development of new chemotherapy and radiotherapy treatments for cancer.

Nicola Jane Curtin, Ph.D. is Professor of Experimental Cancer Therapeutics at Newcastle University. Dr. Curtin is also the team leader for DNA damage signalling and repair projects within CR-UK Drug Development Programme.Ricky Sharma is Associate Professor at the University of Oxford and Honorary Consultant in Clinical Oncology at the Oxford University Hospitals NHS Trust. He graduated in medicine from the University of Cambridge, and subsequently trained in toxicology, general internal medicine, medical oncology and clinical oncology in Cambridge, Glasgow, Leicester and London. Since 2006, he has led a translational research group at the University of Oxford focussed on DNA damage repair and the development of new chemotherapy and radiotherapy treatments for cancer.

Section 1: What PARP is and What it Does             1.       History of the discovery of poly (ADP-ribose) Takashi Sugimura and Sydney Shall2.       Discovery of the PARP superfamily and focus on the lesser exhibited but not lesser talented membersEléa Héberlé, Jean-Christophe Amé, Giuditta Illuzzi, Françoise Dantzer, Valérie Schreiber3.       The role of PARPs in DNA Strand Break RepairStuart L. Rulten, Françoise Dantzer and Keith W. Caldecott4.       TIPs: Tankyrase Interacting ProteinsSusan Smith5.       PARP and CarcinogenesisJunhui Wang, Akira Sato, Hiroaki Fujimori, Yoshio Miki, Mitsuko Masutani6.       Multitasking roles for poly(ADP-ribosyl)ation in aging and longevityAswin Mangerich and Alexander BürkleSection 2. NAD catalysis and the identification of inhibitors           7.       Overview of PARP Inhibitor Design and OptimizationDana Ferraris8.       Structure Based Design of PARP Inhibitors           Stacie S. CananSection 3. Chemo- and radiosensitisation in vitro and in vivo        9.       Preclinical chemosensitization by PARP inhibitorsDavid R. Shalinsky, Cherrie K. Donawho. Gerrit Los, and Joanne P. Palma10.   Classification of PARP inhibitors based on PARP trapping and catalytic inhibition, and rationale for combinations with topoisomerase I inhibitors and alkylating agentsJunko Murai and Yves Pommier11.   Radiosensitisation by poly(ADP-ribose) polymerase inhibitionCharles Fouillade, Alexis Fouquin, Mohammed-Tayyib Boudra, Vincent Favaudon, Vincent Pennaneach, Janet Hall12.   The vasoactivity of PARP inhibitorsCian M. McCrudden and Kaye J. WilliamsSection 4. Synthetic lethality       13.   Synthetic lethality with Homologous Recombination Repair defectsHelen E. Bryant, Sydney Shall14.   Targeting tumour hypoxia with PARP Inhibitors: Contextual synthetic lethalityKatarzyna B. Leszczynska, Nadya Temper, Robert G. Bristow and Ester M. Hammond15.   Other determinants of sensitivity             Naoyuki Okita and Atsushi Shibata16.   Synthetic sickness with molecularly targeted agents against the EGFR pathwayJennifer A. Stanley and Eddy S Yang17.   Disruption of DNA repair by cell cycle and transcriptional CDK inhibitionLiam Cornell, Neil Johnson and Geoffrey I. Shapiro18.   Resistance to PARP Inhibitors Mediated by Secondary BRCA1/2 MutationsKiranjit K. Dhillon and Toshiyasu Taniguchi 19.   PARP inhibitor resistance - what is beyond BRCA1 or BRCA2 restorationGuotai Xu, Jos Jonkers, Sven RottenbergSection 5. Clinical status                20.   Introduction to PARPi clinical trials and future directionsRuth Plummer and Yvette Drew21.   Clinical trials investigating PARP inhibitors as single agentsSheeba Irshad and Andrew Tutt22.   Clinical trials of PARP inhibitors with chemotherapyAshley K. Clift, Nicholas Coupe and Mark R. Middleton23.   Combination of PARP inhibitors with clinical radiotherapyRoss Carruthers, Anthony J. Chalmers24.   Biomarkers for PARP InhibitorsC. Dearman, Ricky A. Sharma, Nicola Curtin

Erscheint lt. Verlag 13.6.2015
Reihe/Serie Cancer Drug Discovery and Development
Cancer Drug Discovery and Development
Zusatzinfo XIX, 591 p. 108 illus., 85 illus. in color.
Verlagsort Cham
Sprache englisch
Themenwelt Medizin / Pharmazie Studium
Naturwissenschaften Biologie
Technik
Schlagworte antibacterial drug resistance • Cancer • Carcinogenesis • DNA repair • drug resistance • Inhibitors • PARP
ISBN-10 3-319-14151-1 / 3319141511
ISBN-13 978-3-319-14151-0 / 9783319141510
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