RB1 and neoplasm: A hallmark of solid tumor types with the losses of tumor suppressors RB1 and/or TP53 are features of high replication stress, genomic instability, mitotic/proliferative indices, and general transient sensitivity to DNA damaging chemotherapy.62,182–184 The list of therapeutic targets exploiting vulnerabilities in replication stress is ever-expanding, but in general, can be grouped into agents that impact DNA fidelity directly (i.e., GC-groove binding agent lurbinectedin185) or indirectly (i.e., DNA damage signaling and repair machinery).