Synthetic lethality: The road to novel therapies for breast cancer

Abstract

When the BRCA1 and BRCA2 tumour 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 a BRCA gene mutation could be tested for the presence of a mutation and their risk of developing cancer could be predicted. Over time though, the discovery of BRCA1 and BRCA2 has had a much greater influence than many might have imagined. In this review, we discuss how the discovery of BRCA1 and BRCA2 has not only provided an understanding of the molecular processes that drive tumourigenesis but also reignited an interest in therapeutically exploiting loss-offunction alterations in tumour suppressor genes.