Objective To systematically summarize the molecular mechanism of aberrant activation of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) signaling pathways in cholangiocarcinoma and the advances in targeted therapy resistance. Method Recent studies on mechanisms of EGFR/HER2 pathway activation, the molecular basis of drug resistance, and novel therapeutic strategies of cholangiocarcinoma were summarized. Results The EGFR/HER2 pathway is aberrantly activated in cholangiocarcinoma through multi-layered mechanisms, including gene mutations, protein overexpression, and sustained activation of downstream pathways. Resistance is characterized by the coexistence of primary and acquired resistance. High molecular heterogeneity and immunosuppressive tumor microenvironment further consolidating the resistant state. Current strategies to overcome resistance focus on combined targeted and immunotherapeutic strategies as well as individualized precision therapy. Conclusions In-depth analysis of the EGFR/HER2 pathway regulatory network, develop combined targeted strategies and establish a dynamic molecular monitoring system are key directions which can break through resistance dilemma and achieve precision therapy.
Citation：
WANG Rui, LIU Guijie. Advances in the aberrant activation of the EGFR/HER2 signaling pathway and resistance mechanisms to targeted therapy in cholangiocarcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(7): 995-1001. doi: 10.7507/1007-9424.202603100
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Copyright ? the editorial department of CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY of West China Medical Publisher. All rights reserved
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