Main description:

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.

Contents:

Section 1: What PARP is and What it Does

1. History of the discovery of poly (ADP-ribose)

Takashi Sugimura and Sydney Shall

2. Discovery of the PARP superfamily and focus on the lesser exhibited but not lesser talented members

Elea Heberle, Jean-Christophe Ame, Giuditta Illuzzi, Francoise Dantzer, Valerie Schreiber

3. The role of PARPs in DNA Strand Break Repair

Stuart L. Rulten, Francoise Dantzer and Keith W. Caldecott

4. TIPs: Tankyrase Interacting Proteins

Susan Smith

5. PARP and Carcinogenesis

Junhui Wang, Akira Sato, Hiroaki Fujimori, Yoshio Miki, Mitsuko Masutani

6. Multitasking roles for poly(ADP-ribosyl)ation in aging and longevity

Aswin Mangerich and Alexander BurkleSection 2. NAD catalysis and the identification of inhibitors

7. Overview of PARP Inhibitor Design and Optimization

Dana Ferraris

8. Structure Based Design of PARP Inhibitors

Stacie S. Canan

Section 3. Chemo- and radiosensitisation in vitro and in vivo

9. Preclinical chemosensitization by PARP inhibitors

David R. Shalinsky, Cherrie K. Donawho. Gerrit Los, and Joanne P. Palma

10. Classification of PARP inhibitors based on PARP trapping and catalytic inhibition, and rationale for combinations with topoisomerase I inhibitors and alkylating agents

Junko Murai and Yves Pommier

11. Radiosensitisation by poly(ADP-ribose) polymerase inhibition

Charles Fouillade, Alexis Fouquin, Mohammed-Tayyib Boudra, Vincent Favaudon, Vincent Pennaneach, Janet Hall

12. The vasoactivity of PARP inhibitors

Cian M. McCrudden and Kaye J. Williams

Section 4. Synthetic lethality

13. Synthetic lethality with Homologous Recombination Repair defects

Helen E. Bryant, Sydney Shall

14. Targeting tumour hypoxia with PARP Inhibitors: Contextual synthetic lethality

Katarzyna B. Leszczynska, Nadya Temper, Robert G. Bristow and Ester M. Hammond

15. Other determinants of sensitivity

Naoyuki Okita and Atsushi Shibata

16. Synthetic sickness with molecularly targeted agents against the EGFR pathway

Jennifer A. Stanley and Eddy S Yang

17. Disruption of DNA repair by cell cycle and transcriptional CDK inhibition

Liam Cornell, Neil Johnson and Geoffrey I. Shapiro

18. Resistance to PARP Inhibitors Mediated by Secondary BRCA1/2 Mutations

Kiranjit K. Dhillon and Toshiyasu Taniguchi

19. PARP inhibitor resistance - what is beyond BRCA1 or BRCA2 restoration

Guotai Xu, Jos Jonkers, Sven Rottenberg

Section 5. Clinical status

20. Introduction to PARPi clinical trials and future directions

Ruth Plummer and Yvette Drew

21. Clinical trials investigating PARP inhibitors as single agents

Sheeba Irshad and Andrew Tutt

22. Clinical trials of PARP inhibitors with chemotherapy

Ashley K. Clift, Nicholas Coupe and Mark R. Middleton

23. Combination of PARP inhibitors with clinical radiotherapy

Ross Carruthers, Anthony J. Chalmers

24. Biomarkers for PARP Inhibitors

C. Dearman, Ricky A. Sharma, Nicola Curtin