ABSTRACT
A greater understanding of DNA repair pathways offers the tantalizing prospect of the development of novel agents designed to inhibit these repair processes. Cells are reliant on specifi c DNA repair pathways for their recovery from chemotherapy and radiotherapy-induced DNA damage (see Chapter 1). Hence inhibition of DNA repair should improve the effi cacy of current therapies and offer the potential to exploit the genetic differences between normal and malignant cells. It is becoming clear that the successful transition from a promising pre-clinical DNA repair inhibitor to mainstream clinical usage is a process fraught with complexity. In this Chapter, we examine the questions that some recent early phase trials of DNA repair inhibitors have attempted to answer. The limitations inherent in the design of the trials are discussed. We analyze the results, dissect the lessons learnt and address some of the pitfalls in their interpretation. Finally, we offer guidelines for the future design of early phase clinical trials of DNA repair inhibitors.
