Characterization of ROS-1 Fusion Proteins in Non-Small Cell Lung Cancer

Cancer is the uncontrolled division of cells that is accompanied by alterations of the human genome. Among these alterations is the formation of pathogenic fusion proteins. Fusion proteins occur when two genes, originally separated, are fused to a single unit with unique functional properties that favor the survival, proliferation and metastasis of malignant cells. In our lab, we focus on the structural and functional characterization of ROS-1 fusions, one of the largest and most lethal fusion families. The ROS-1 fusion family has been linked primarily to non-small cell lung cancer (NSCLC) and secondary to brain, soft tissue, gastric, and liver cancer. ROS-1 fusion proteins are mainly found in adult patients with NSCLC and to a lesser extent in pediatric patients. Currently, available therapeutics target the ROS-1 portion of the fusion protein, but drug resistance is usually acquired, rendering these drugs useless after initial treatment. Drugs that target the other member of ROS-1 fusion proteins are not readily available but could potentially target the fusion protein with higher specificity, as ROS-1 shares similar topology with many other kinases. Structural and functional characterization of ROS-1 fusion proteins, with emphasis on the fusion partner, will permit the design and development of new generation therapeutic with antitumor properties