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 repair of DNA damage24, 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. Here, PKMYT1 is linked to neoplasm.