RB1 and neoplasm: The genetic lesions causing the frequent functional inactivation of pRB in tumors create two different types of challenges: In cells where RB1 is mutated, the challenge is to identify features that distinguish RB1 mutant cells from normal cells and represent points of vulnerability that can be exploited; in tumors where pRB is present but functionally inactivated, there is an additional possibility to reactivate the latent tumor-suppressive properties of pRB.