The loss of Rb is related to the overexpression of E2F.[19] Different studies have shown that E2F inhibits miR-223 transcription by combining with its promoter, suggesting that E2F1 can be used as miR-223 gene, and inhibition of miR-223 is a common feature in the process of cancer progression.[32] E2F amplification allowed it to bypass CDK4/6i and block the cyclin pathway, leading to cancer progression after CDK4/6i treatment. This evidence concerns the gene CDK4 and cancer.