Synthetic lethal approaches to the development of new therapies for cancer


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Alan Ashworth
Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK

Abstract

<p>Many tumours harbour defects in their ability to maintain genomic integrity. This contributes to the mutational burden and likely fosters pathogenesis. We have been exploring therapeutic strategies to exploit these defects. We have used a synthetic lethal approach to target the defect in DNA repair by homologous recombination in tumours with a <i>BRCA1</i> or <i>BRCA2</i> mutation. This strategy using PARP inhibitors is showing considerable promise in the clinic. Here, I will describe the approach as well recent work defining determinants of sensitivity and resistance to PARP inhibitors. The application of the synthetic lethal approach to other cancer types will also be discussed. </p><i>Declaration of competing interest for Alan Ashworth: Professor Ashworth may benefit financially from the development of PARP inhibitors through patents held with KuDOS–AstraZeneca through the Institute of Cancer Research “rewards to inventors” scheme.</i><br>