Our work documents that enforced RB1 loss causes clinically meaningful sensitivity (i.e. sensitivity akin to that seen in BRCA1,2-defective CAPAN1) in otherwise PARPi insensitive osteosarcoma lines, providing proof of concept for a direct role of RB1 loss in the selective PARPi sensitivity observed. The gene discussed is RB1; the disease is osteosarcoma.