Open Access

REVIEW

Emerging HER2 Targeting Immunotherapy for Cholangiocarcinoma

Prin Sungwan¹, Jutatip Panaampon^1,2, Ratchaneewan Sumankan^1,3, Genki Aoki¹, Seiji Okada^1,*

1 Division of Hematopoiesis, Joint Research Center for Human Retrovirus Infection & Graduate School of Medical Sciences, Kumamoto University 2-2-1 Honjo, Chuo-ku, Kumamoto, 860-0811, Japan
2 Division of Hematologic Neoplasia, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA
3 Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand

* Corresponding Author: Seiji Okada. Email:

Oncology Research 2025, 33(9), 2279-2307. https://doi.org/10.32604/or.2025.065319

Received 10 March 2025; Accepted 11 June 2025; Issue published 28 August 2025

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.

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