The biochemical assays revealed that abemaciclib hindered the progression of breast cancer cells MDA-MB-231 and MCF-7 and enhanced RT (10 Gy) by provoking cell cycle arrest throughout the restraint of CDK4 and CDK6 expression and increasing apoptosis, in addition to decreasing the PI3K/AKT/mTOR and NF-κβ/TGF-β pathway expression; inhibiting CK18 and COX2 activity; boosting the protein concentration of BAX and P53; and decreasing Bcl-2, IL-6, IL-1β, MMP2, and MMP9, modulating oxidative stress markers. Here, AKT1 is linked to breast carcinoma.