RB1 and cancer: This strategy has been applied in cancers with high level of CDKN2A deficiency, but further analyses and functional validations will be needed to delineate synthetic lethality associated specifically with ARF deficiency, as most efforts to identify therapeutic opportunities associated with CDKN2A deficiency begin and end at p16-CDK4/6-RB pathway intervention (Oh et al., 2020; Cao et al., 2021; Satpathy et al., 2021).