HSPA5 and hepatocellular carcinoma: Molecular mechanisms involving in resistance to sorafenib revealed by investigators included PI3K/Akt signaling pathway, JAK-STAT pathways, hypoxia-inducible pathways, epithelial-mesenchymal transition [17], [40], a positive modifier GRP78 for sorafenib resistance acquisition in HCC [41], signaling pathways controlled by EGFR and HER-3 restrict sorafenib effects both in naive and sorafenib-resistant HCC cells [42], etc. However, the mechanisms involving in TTK-associated resistance to sorafenib remained unclear.