In the tumor microenvironment, miR-21 derived from macrophages and CAFs are also transferred to cancer cells via EVs, inducing chemoresistance by activating the phosphoinositol 3-kinase (PI3K)/AKT signaling pathway or binding apoptotic peptidase activating factor 1 (APAF1) [83, 85]. This evidence concerns the gene APAF1 and cancer.