IGF-1 and BRCA1 signalling pathways in familial cancer

Summary The insulin-like growth factor (IGF) system has a direct effect on cellular proliferation and survival, and interacts with genetic and environmental factors implicated in causing cancer. Experimental, clinical, and epidemiological evidence show that the IGF signalling pathways are important mediators in the biochemical and molecular chain of events that lead from a phenotypically normal cell to one harbouring neoplastic traits. BRCA1 and BRCA2 have an important role in the development of hereditary and sporadic breast and ovarian cancer. Recent evidence suggests that risk of cancer conferred by BRCA mutations can be modified by genetic and environmental factors, including ambient concentrations of IGF-1 and polymorphisms in IGF system components. This Review addresses interactions between the IGF and BRCA1 signalling pathways, and emphasises the convergence of IGF-1-mediated cell survival, proliferative pathways, and BRCA1-mediated tumour protective pathways. Understanding the complex interactions between these signalling pathways might improve our understanding of basic molecular oncology processes and help to identify new molecular targets, predictive biomarkers, and approaches for optimising cancer therapies.