<b>Conclusions</b>: Our study suggested that CDKN3 acted as an oncogene in human ESCC and may accelerate the G1/S transition by affecting CyclinD-CDK4 complex via regulating pAKT-p53-p21 axis and p27 independent of AKT.
Of additional importance, this combined treatment has potent efficacy in ESCC cells with acquired resistance to CDK4/6 inhibitors in vitro and in xenograft tumors.
CDK4/6 inhibitor-SHR6390 exerted potential antitumor activity against ESCC cell lines and xenografts, and evaluation of CDK6 and Cyclin D1 expressions might be helpful to select patients beneficial from SHR6390, which provided evidences for future clinical trials.