Abstract
Cholangiocarcinoma (CCA) is a fatal bile duct malignancy. CCA is intrinsically resistant to standard chemotherapy, responds poorly to it, and has a poor prognosis. Effective treatments for cholangiocarcinoma remain elusive, and a breakthrough in CCA treatment is still awaited. The human epidermal growth factor receptor 2 (HER2) plays an oncogenic role by promoting an aggressive cancer phenotype through multiple pathways. While HER2 has shown increasing potential as an effective target for breast and gastric cancers over the last decade, this has not been the case for CCA. This review explores the possibility of targeting HER2 in CCA immunotherapy. Key findings suggest that HER2 alterations have been reported as one of the signatures associated with a poorer prognosis in liver fluke-associated CCA, the most prevalent subtype in Southeast Asia. Furthermore, we assess recent advances in HER2-targeted therapeutic approaches, presenting the current stage, rationale, and evidence supporting the use of HER2 as a promising therapeutic target for cancer immunotherapy in CCA. We also emphasize the crucial role of animal models in developing anticancer therapies. In summary, focusing on HER2 expression could provide alternative strategies for the HER2-altered CCA cluster.