SMAD4 and breast cancer: HDAC8 promotes paclitaxel resistance in breast cancer by activating TGF‐β signaling through the SIRT7‐SMAD4 axis.[53] In acute myeloid leukemia (AML), HDAC8 promotes resistance to daunorubicin (DNR) by regulating the expression of IL‐6 and IL‐8.[54] In AML with an internal tandem duplication (ITD) mutation of FMS‐like receptor tyrosine kinase‐3 (FLT3), the use of FLT3 tyrosine kinase inhibitors induces FOXO1‐ and FOXO3‐associated upregulation of HDAC8, thereby inactivating p53 and leading to TKI resistance.[55] Here, we further investigated the role of HDAC8 in ccRCC.