ROS1 kinase as a candidate molecular target in angiosarcoma

Angiosarcomas are an uncommon type of soft tissue tumor, but are clinically aggressive and associated with relatively poor survival. New targets for molecularly-directed therapy are needed. In preliminary genomic analyses, we discovered presumptive oncogenic rearrangements of ROS1, a receptor tyrosine kinase previously linked to a subset of brain and lung tumors, but not to sarcomas. The objectives of the proposed study are to determine whether ROS1 functions as an oncogenic driver in angiosarcoma (by overexpression studies in cultured cells), whether angiosarcomas are addicted to ROS1 (by RNA interference knockdown and small molecule inhibitor studies in cultured cells), and whether ROS1 alterations are frequent in angiosarcoma (by fluorescence in situ hybridization and RNA in situ hybridization analysis of tissue specimens). These studies may define ROS1 as a promising new molecular target for patients with angiosarcoma. Moreover, because a small-molecule inhibitor already exists, positive findings should be rapidly translatable to improved patient management.