Analysis of ctDNA or tumor mRNA from patients enrolled in the PALOMA-3, NeoPalAna and MONALEESA-3 trials have identified Rb mutations, activating mutations in PIK3CA and ESR1, increased cyclin E1 and activation of the PDK1-AKT axis as some of the drivers of resistance [7,9,11]. The gene discussed is PDK1; the disease is neoplasm.