Moreover, a recent study from Thongsom’s group [135] demonstrated that piperlongumine (PL), a naturally-occurring small molecule, could induce CCA cellular apoptosis through ROS-mediated JNK/ERK activation and proteasome inhibition, while the susceptibility of CCA to PL therapy may depend on the activation of AKT. This evidence concerns the gene MAPK8 and cholangiocarcinoma.