We highlight nine potential pharmacological strategies in RB1-deficient cancers: inhibition of spliceosomal mechanisms, Aurora Kinase inhibition, PARP inhibition, ferroptosis induction, SKP2 ubiquitin ligase inhibition, histone demethylase LSD1 inhibition, histone methyltransferase DOT1L inhibition, ESRRG inhibition, and arginine methyltransferase PRMT5 inhibition. The gene discussed is ESRRG; the disease is cancer.