Balasubramanian Brinda, Venkatraman Simran, Myint Kyaw Zwar, Janvilisri Tavan, Wongprasert Kanokpan, Kumkate Supeecha, Bates David O, Tohtong Rutaiwan
Graduate Program in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
Pharmaceuticals (Basel). 2021 Jan 11;14(1):51. doi: 10.3390/ph14010051.
Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available. Despite the increasing numbers of clinical studies in CCA, targeted therapy drugs rarely get approved for clinical use. In this review, we discuss the shortcomings of the conventional clinical trial process and propose the implementation of a novel concept, co-clinical trials to expedite drug development for CCA patients. In co-clinical trials, the preclinical studies and clinical trials are conducted simultaneously, thus enabling real-time data integration to accurately stratify and customize treatment for patients, individually. Hence, co-clinical trials are expected to improve the outcomes of clinical trials and consequently, encourage the approval of targeted therapy drugs. The increased availability of targeted therapy drugs for treatment is expected to facilitate the application of precision medicine in CCA.
胆管癌（CCA）是一组起源于胆道的恶性肿瘤，其死亡率高，全球发病率呈令人担忧的上升趋势。在CCA发病率最高的泰国，社会经济负担沉重。然而，治疗选择有限，手术切除是唯一具有治愈意图的治疗方式。目前的标准治疗仍然是辅助化疗和姑息化疗，而这对大多数患者无效。即使经过手术切除，总体生存率依然很低，而且肿瘤异质性使治疗进一步复杂化。这些因素共同使得CCA成为东南亚地区的一个重大负担。为了有效管理CCA，治疗必须针对每个患者量身定制，为此必须有各种各样的靶向治疗方法。尽管CCA的临床研究数量不断增加，但靶向治疗药物很少获得临床使用批准。在本综述中，我们讨论了传统临床试验过程的缺点，并提出实施一种新概念——联合临床试验，以加快针对CCA患者的药物开发。在联合临床试验中，临床前研究和临床试验同时进行，从而能够进行实时数据整合，为患者准确分层并量身定制治疗方案。因此，联合临床试验有望改善临床试验结果，进而促使靶向治疗药物获得批准。预计治疗用靶向治疗药物可用性的提高将促进精准医学在CCA中的应用。
