From our relatively unbiased analysis of genome-scale shRNA screens, it is perhaps striking that many of the highly penetrant Rb synthetic lethal effects we identified (e.g., SKP1, SKP2, CKS1B, COPS1, COPS2 and COPS3) have two characteristics: (i) they are closely, rather than distally, involved in controlling an essential process in highly proliferating tumour cells, namely G1 cell cycle progression by Cyclin/CDK activity; and (ii) this process is also closely, rather than distally, controlled by the synthetic lethal partner, Rb. The gene discussed is RB1; the disease is neoplasm.