Given CCNE1-amplified cells rely on the G2/M checkpoint to attenuate lethal levels of replication stress-induced DNA damage by upregulating the ATR axis for DNA repair24, we hypothesized that dual inhibition of PKMYT1 and ATR (PKMYT1i-ATRi) will further enhance CDK1 activation and cytotoxicity, especially towards CCNE1 amplified or overexpressing tumor cells allowing lower dosing strategies and potentially alleviate toxicity. The gene discussed is CDK1; the disease is neoplasm.