Genome-Wide Profiling of Laron Syndrome Patients Identifies Novel Cancer Protection Pathways

Abstract

Laron syndrome (LS), or primary growth hormone resistance, is a prototypical congenital insulin-like growth factor 1 (IGF1) deficiency. The recent epidemiological finding that LS patients do not develop cancer is of major scientific and clinical relevance. Epidemiological data suggest that congenital IGF1 deficiency confers protection against the development of malignancies. This ‘experiment of nature’ reflects the critical role of IGF1 in tumor biology. The present review article provides an overview of recently conducted genome-wide profiling analyses aimed at identifying mechanisms and signaling pathways that are directly responsible for the link between life-time low IGF1 levels and protection from tumor development. The review underscores the concept that ‘data mining’ an orphan disease might translate into new developments in oncology.

Keywords

• insulin-like growth factor 1 (IGF1)
• IGF1 receptor (IGF1R)
• growth hormone receptor (GH-R)
• Laron syndrome
• cancer protection
• thioredoxin-interacting protein (TXNIP)