In this context, downregulation of circ_0000338 through the exosomal delivery of sh‐circ_0000338 successfully reversed 5‐FU resistance.[100] MiR‐21 is also known to promote 5‐FU resistance in CRC by downregulating the expression of human DNA MutS homolog 2 (hMSH2).[101] In a study conducted by Liang et al., exosomes were engineered to co‐deliver 5‐FU and a miR‐21 inhibitor to 5‐FU‐resistant CRC cells. This evidence concerns the gene MSH2 and colorectal carcinoma.