下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:Advances in target drugs and immunotherapy for biliary tract cancer.
在专家意见中,我们讨论了符合靶向治疗条件的患者稀缺这一问题,以及如何设计临床试验来克服这一挑战。
引言:胆道癌(BTC)治疗多年进展停滞后,靶向治疗和免疫治疗的出现带来了显著转变,推动了这一侵袭性疾病治疗的实质性进展。 综述范围:我们全面概述已纳入BTC治疗流程的靶向疗法,例如FGFR、IDH和HER2抑制剂。此外,还深入讨论正在研究但相对不为人熟知的靶点,包括KRAS原癌基因、MAPK级联、PI3K/AKT/mTOR通路,以及针对p53、紧密连接蛋白、组蛋白和线粒体代谢的新型分子。我们还讨论不依赖特定组织来源的药物,并分析专门针对BTC的可用疗效数据。此外,我们考察不断扩展的免疫治疗领域,关注免疫检查点抑制剂的应答预测因素,以及嵌合抗原受体(CAR)T细胞和疫苗等新型免疫药物。 专家观点:本文讨论符合靶向治疗条件的患者数量稀少这一问题,以及如何设计临床试验以克服这一挑战。我们还总结了最有前景的试验,这些试验有望改变免疫治疗和靶向药物的临床实践。
INTRODUCTION: After years of treatment stagnation in biliary tract cancers (BTC), there has been a notable shift with the emergence of targeted therapies and immunotherapy, leading to substantial progress in tackling this aggressive disease. AREAS COVERED: We provide a comprehensive overview of the target therapies that are already part of the treatment algorithm for BTC, such as FGFR, IDH, and HER2 inhibitors. Additionally, we delve into some less known targets that are being explored, such as KRAS proto-oncogene, MAPK cascade, PI3K/AKT/mTOR pathway and novel molecules directed against P53, claudin, histones, and mitochondrial metabolism. Furthermore, we discuss agnostic drugs and analyze the efficacy data available for BTC specifically. We also examine the expanding world of immunotherapy, with an eye on predictive factors of response for immune checkpoint inhibitors, and on novel immune drugs such as chimeric antigen receptor (CAR)-T and vaccines. EXPERT OPINION: In the expert opinion, we discuss the problem of the scarcity of patients eligible for target therapies and how can clinical trials be designed to overcome this challenge. We also summarize the most promising trials that have the potential to change clinical practice both for immunotherapies and target drugs.
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