Targeting the DNA Damage Response for Anti-Cancer Therapy

John Pollard is Vice President, Principal Research Fellow and Head of Biological Sciences at Vertex Pharmaceuticals’ UK research site. John joined Vertex in 1999 following a PhD at Southampton University and Postdoctoral positions at St. Andrews and Birmingham Universities in bioorganic chemistry. During his tenure at Vertex, John has led a series of oncology research and development projects across cell cycle control, survival and growth, and most recently DNA damage, which together have yielded multiple clinical candidates. John has served as global research lead for Vertex’s oncology effort and led numerous collaborations with academic groups and pharma companies.Nicola Curtin is Professor of Experimental Cancer Therapeutics at Newcastle University, UK. After obtaining her Ph.D. in hepatocarcinogenesis from the University of Surrey she started working at Newcastle University, initially exploring novel therapies for liver cancer, then the cytotoxic mechanisms of novel antifolates and the role of nucleoside transport. Prof Curtin was a founding member of the Newcastle Anticancer Drug Discovery Initiative and contributed to the development of PARP inhibitors, including the identification of their synthetic lethality in cells lacking homologous recombination function. Her work focusses on the DNA damage response in general and she has also worked on the preclinical development of ATM, ATR and DNA-PK inhibitors for the treatment of cancer. In addition, she undertakes translational studies to identify pharmacodynamic biomarkers and those predictive of response to DDR-inhibitor therapy in cultured cells and patient material. She’s also the co-editor of PARP Inhibitors for Cancer Therapy in this series.

“The book provides up to date and comprehensive review of hot topic in the field cancer drug discovery and development and represents a promising therapeutic strategy for cancer patients. It is the source of valuable information for people working in science and oncology clinics.” (Jela Brozmanova, Neoplasma, Vol. 65 (06), 2018)

• 1. Targeting DNA repair in anti-cancer treatments.- 2. The DNA damage response: roles in cancer etiology and treatment.- 3. Control of DNA Replication by ATR.- 4. Targeting ATR for cancer therapy: Profile & expectations for ATR inhibitors.- 5. Targeting ATR for cancer therapy: ATR-targeted drug candidates.- 6. ATM: its recruitment, activation, signalling and contribution to tumour suppression.- 7. Pre-clinical profile and expectations for pharmacological ATM inhibition.- 8. Targeting ATM for cancer therapy: Prospects for drugging ATM.- 9. Targeting Chk1 for cancer therapy: rationale, progress and prospects.- 10. Preclinical profiles and contexts for CHK1 and CHK2 inhibitors.- 11. Clinical development of CHK1 inhibitors.- 12. Established and emerging roles of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs).- 13. Targeting DNA-PK as a therapeutic approach in oncology.- 14. Dbait: a new concept of DNA repair pathways inhibitor from bench to bedside.- 15. Alternative Non Homologous End-joining: Mechanisms and Targeting Strategies in Cancer.