医学
恶性肿瘤
胆囊癌
胆道癌
癌症
靶向治疗
胆道
化疗
药物重新定位
抗药性
肿瘤科
药品
生物信息学
内科学
吉西他滨
药理学
生物
微生物学
作者
Christian Mayr,Tobias Kiesslich,Dominik Paul Modest,Sebastian Stintzing,Matthias Ocker,Daniel Neureiter
标识
DOI:10.1080/13543784.2022.2034785
摘要
Biliary tract cancer (BTC), including intra- and extrahepatic cholangiocarcinoma and gallbladder cancer, is a rare and highly difficult to manage human malignancy. Besides late diagnosis and associated unresectability, frequently observed unresponsiveness toward and recurrence following chemotherapy or targeted therapy essentially contribute to the dismal prognosis of BTC patients.The review provides an update on individual mechanisms involved resistance of BTC toward conventional chemotherapy as well as targeted therapies. We review the distinct mechanisms of pharmacoresistance (MPRs) which have been defined in BTC cells on a molecular basis and examine the specific consequences for the various approaches of chemo-, targeted or immunomodulatory therapies.Based on currently available experimental and clinical data, the present knowledge about these MPRs in BTCs are summarized. While some possible tactics for overcoming these mechanisms of resistance have been investigated, a BTC-specific and efficient approach based on comprehensive in vitro and in vivo experimental systems is not yet available. Additionally, a reliable monitoring of therapy-relevant cellular changes needs to be established which allows for choosing the optimal drug (combination) before and/or during pharmacological therapy.
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