Zheng Qingfan, Zhang Bin, Li Changfeng, Zhang Xuewen
Department of Hepatobiliary and Pancreas Surgery, the Second Hospital of Jilin University, Changchun, China.
Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, China.
Front Oncol. 2022 Mar 17;12:850732. doi: 10.3389/fonc.2022.850732. eCollection 2022.
Cholangiocarcinoma (CCA) is an aggressive tumor characterized by a poor prognosis. Therapeutic options are limited in patients with advanced stage of CCA, as a result of the intrinsic or acquired resistance to currently available chemotherapeutic agents, and the lack of new drugs entering into clinical application. The challenge in translating basic research to the clinical setting, caused by preclinical models not being able to recapitulate the tumor characteristics of the patient, seems to be an important reason for the lack of effective and specific therapies for CCA. So, there seems to be two ways to improve patient outcomes. The first one is developing the combination therapies based on a better understanding of the mechanisms contributing to the resistance to currently available chemotherapeutic agents. The second one is developing novel preclinical experimental models that better recapitulate the genetic and histopathological features of the primary tumor, facilitating the screening of new drugs for CCA patients. In this review, we discussed the evidence implicating the mechanisms underlying treatment resistance to currently investigated drugs, and the development of preclinical experiment models for CCA.
胆管癌（CCA）是一种侵袭性肿瘤，预后较差。由于对目前可用化疗药物存在内在或获得性耐药，且缺乏进入临床应用的新药，晚期CCA患者的治疗选择有限。临床前模型无法重现患者的肿瘤特征，这导致基础研究向临床应用转化面临挑战，这似乎是CCA缺乏有效和特异性治疗方法的一个重要原因。因此，似乎有两种方法可以改善患者预后。第一种是在更好地理解导致对目前可用化疗药物耐药的机制的基础上开发联合疗法。第二种是开发新型临床前实验模型，更好地重现原发性肿瘤的基因和组织病理学特征，便于为CCA患者筛选新药。在这篇综述中，我们讨论了与目前所研究药物治疗耐药机制相关的证据，以及CCA临床前实验模型的发展。
