Curtin N.J., Sharma R.A. (Eds.) PARP Inhibitors for Cancer Therapy

Cham, Switzerland: Humana Press, 2015. — 591 p. — (Cancer Drug Discovery and Development 83). — ISBN: 978-3-319-14150-3, 978-3-319-14151-0.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.What Parp is and What it Does
History of the Discovery of Poly (ADP-ribose)
Discovery of the PARP Superfamily and Focus on the Lesser Exhibited But Not Lesser Talented Members
The Role of PARPs in DNA Strand Break Repair
TIPs: Tankyrase Interacting Proteins
PARP and Carcinogenesis
Multitasking Roles for Poly(ADP-ribosyl)ation in Aging and LongevityNAD Catalysis and the Identification of Inhibitors
Overview of PARP Inhibitor Design and Optimization
Structure Based Design of PARP InhibitorsChemo- and Radiosensitisation in Vitro and in Vivo
Preclinical Chemosensitization by PARP Inhibitors
Classification of PARP Inhibitors Based on PARP Trapping and Catalytic Inhibition, and Rationale for Combinations with Topoisomerase I Inhibitors and Alkylating Agents
R adiosensitisation by Poly(ADP-ribose) Polymerase Inhibition
The Vasoactivity of PARP InhibitorsSynthetic Lethality
Synthetic Lethality with Homologous Recombination
Repair Defects
Targeting Tumour Hypoxia with PARP Inhibitors: Contextual Synthetic Lethality
Other Determinants of Sensitivity
Synthetic Sickness with Molecularly Targeted Agents Against the EGFR Pathway
Disruption of DNA Repair by Cell Cycle and Transcriptional CDK Inhibition
R esistance to PARP Inhibitors Mediated by Secondary BRCA1/2 Mutations
PARP Inhibitor Resistance — What Is Beyond BRCA1 or BRCA2 Restoration?Clinical Status
Introduction to PARPi Clinical Trials and Future Directions
Clinical Trials Investigating PARP Inhibitors as Single Agents
Clinical Trials of PARP Inhibitors with Chemotherapy
Combination of PARP Inhibitors with Clinical Radiotherapy
Biomarkers for PARP Inhibitors