Synthetic lethality: the road to novel therapies for breast cancer

Abstract

When theBRCA1andBRCA2tumour suppressor genes were identified in the early 1990s, the immediate implications of mapping, cloning and delineating the sequence of these genes were that individuals in families with aBRCAgene mutation could be tested for the presence of a mutation and their risk of developing cancer could be predicted. Over time though, the discovery ofBRCA1andBRCA2has had a much greater influence than many might have imagined. In this review, we discuss how the discovery ofBRCA1andBRCA2has not only provided an understanding of the molecular processes that drive tumourigenesis but also reignited an interest in therapeutically exploiting loss-of-function alterations in tumour suppressor genes.