Synthetic lethal metabolic targeting of cellular senescence in cancer therapy

In mice with Eµ-myc transgenic lymphomas in which therapy-induced senescence (TIS) depends on the H3K9 histone methyltransferase Suv39h1, TIS-competent lymphomas but not TIS-incompetent Suv39h1– lymphomas show increased glucose utilization and ATP production after senescence-inducing chemotherapy to cope with proteotoxic stress elicited by factors of the senescence-associated secretory phenotype (SASP); senescent cancers are selectively vulnerable to drugs that block glucose utilization or autophagy.