The ROS1 receptor family

Abstract

The proto-oncogene receptor tyrosine kinase ROS1 is an evolutionarily conserved receptor that functions in development and cancer. Using genetic models and biochemical approaches, ROS1 was shown to play distinctive roles in epithelial cell differentiation during the development of a variety of organs. Although substantial, these advances remain hampered by the absence of an identified ligand, making ROS1 one of the last two remaining orphan receptor tyrosine kinases. Recent global in-depth cancer genomic studies have unveiled a variety of different chromosomal rearrangements that leads to the oncogenic activation of ROS1. Studies on the resulting ROS1 fusion kinases have shed light on the molecular mechanisms underlying ROS1 transforming activities. ROS1 and its oncogenic fusion variants therefore constitute clinically relevant targets for cancer therapeutic intervention. This chapter highlights the various roles that this receptor plays in multiple system networks in normalcy and disease and points to future directions towards the elucidation of ROS1 function in the context of ligand identification, signaling pathways and clinical applications.