POLE and neoplasm: Either alterations that are compelling targets for tumor-agnostic treatment approaches, such as the RET mutations and ERBB2 amplifications found in C2, or alterations that are linked with defective DNA repair mechanisms, such as the mutations of distinct genes involved in HRR verified in C1, C3 and C4 and the mutations of POLE documented in C2 and C3, and a vast array of other specific alterations (some of them never previously documented in DDLPS, LMS and UPS) confer sensitivity to a broad spectrum of different agents.