Studies in ERα+ endocrine-resistant and CDK4/6-inhibitor-resistant MCF7 and T47D breast cancer cells, targeting the G2/M checkpoint, showed that Adavosertib significantly decreased cell proliferation and increased G2/M arrest, apoptosis, and γ-H2AX levels (a marker for DNA double-stranded breaks) in resistant cells compared with sensitive cells. Here, CDK4 is linked to breast cancer.