 This study suggests that targeting both the CDK4,6 and PI3KMTOR pathways may be beneficial in treating intrahepatic cholangiocarcinoma, ICCA. It found that the combination of two drugs, palbaciclimb, a CDK4,6 inhibitor, and PF04691502, a PI3KMTOR inhibitor, can effectively inhibit the proliferation, migration, and invasion of ICCA cells. This combination therapy also demonstrated greater stability in reducing tumor growth than either drug alone. Additionally, it was found that the combination had a stronger effect on the downstream signaling pathways of CCND1, CDK4,6, and PI3KMTOR than either drug alone. These findings suggest that dual inhibition of these pathways may be a promising strategy for treating ICCA. This article was authored by Jepeng Lee, Huishin Zhu, Ji Jiashia, and others.