Camera Silvia, Rossari Federico, Foti Silvia, Vitiello Francesco, Persano Mara, Prinzi Federica Lo, De Cobelli Francesco, Aldrighetti Luca, Cascinu Stefano, Rimini Margherita, Casadei-Gardini Andrea
Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, via Olgettina 60, 20132, Milan, Italy.
San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy.
Target Oncol. 2025 Mar;20(2):269-280. doi: 10.1007/s11523-025-01132-w. Epub 2025 Feb 22.
Biliary tract cancers (BTCs) are a wide class of malignancies with dismal prognosis. The therapeutic scenario of metastatic BTCs has profoundly changed during recent years. The combination of cisplatin-gemcitabine plus immunotherapy is currently the gold standard in the first line. The more extensive comprehension of the mechanisms at the basis of BTCs and the identification of several molecular alterations has led to the introduction of target-directed therapies in the second line and beyond that have expanded the therapeutic armamentarium alongside the standard FOLFOX regimen, and for the near future, the results of some trials with targeted therapies in first line are expected. HER2 represents a promising therapeutic target detected in BTCs, being overexpressed in approximately 15-20% of cases, with a strong predilection for gallbladder carcinoma and extrahepatic cholangiocarcinoma, although a small proportion of HER2 overexpression can be detected even in intrahepatic cholangiocarcinoma. The efficacy and safety of different HER2 inhibitors have been investigated in several studies in the second line and beyond with encouraging results. This comprehensive review is intended to provide a summary of existing evidence and future perspectives on HER2 altered BTCs.
胆道癌（BTCs）是一类预后不佳的恶性肿瘤。近年来，转移性BTCs的治疗情况发生了深刻变化。顺铂-吉西他滨联合免疫疗法目前是一线治疗的金标准。对BTCs基础机制的更深入理解以及多种分子改变的发现，促使二线及以后引入了靶向治疗，这些治疗与标准的FOLFOX方案一起扩大了治疗手段，并且在不久的将来，预计一线靶向治疗的一些试验结果也会出现。HER2是在BTCs中检测到的一个有前景的治疗靶点，在大约15%-20%的病例中过度表达，对胆囊癌和肝外胆管癌有强烈偏好，尽管即使在肝内胆管癌中也能检测到一小部分HER2过度表达。在多项二线及以后的研究中对不同HER2抑制剂的疗效和安全性进行了调查，结果令人鼓舞。这篇综述旨在总结关于HER2改变的BTCs的现有证据和未来前景。
