23. Combination of PARP Inhibitors with Clinical Radiotherapy
Authors: Ross Carruthers, Anthony J Chalmers
Publisher: Springer International Publishing
Radiosensitisation of solid tumours by manipulation of the DNA damage response offers an opportunity to increase the effectiveness of radiotherapy in terms of enhanced local tumour control, better alleviation of symptoms and improved cure rates. PARP inhibitors are the best characterised DNA damage response inhibitors and possess many qualities that predict clinical utility as radiosensitisers. Pre-clinical data indicate that PARP inhibitors will provide tumour specific radiosensitisation and may be effective radiosensitisers of hypoxic tumour cells and cancer stem cells. They have minimal systemic toxicity as single agents and if combined with modern radiotherapy technology are likely to have acceptable ‘in-field’ toxicity. As such, they represent ideal candidate radiosensitisers for development in clinical trials. Significant challenges and opportunities exist in designing appropriate clinical trials that will assess toxicity and benefit from these agents in a rigorous manner. This chapter reviews the clinical rationale for the use of PARP inhibitors as radiosensitisers and summarises their current clinical development.