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胆囊癌的靶向治疗:临床前和临床开发中药物的概述。

Targeted therapies for gallbladder cancer: an overview of agents in preclinical and clinical development.

机构信息

Oncology Unit, Azienda USL Bologna, Bologna, Italy.

Medical Oncology Unit, University Hospital of Parma, Parma, Italy.

出版信息

Expert Opin Investig Drugs. 2021 Jul;30(7):759-772. doi: 10.1080/13543784.2021.1928636. Epub 2021 May 17.

DOI:10.1080/13543784.2021.1928636
PMID:33966562
Abstract

: Gallbladder cancer (GC) is a rare malignancy with a dismal prognosis. When diagnosed early enough, it can be cured by surgical removal. Unfortunately, only few GC patients can be amenable to surgery, though, with a high relapse rate. Conventional chemotherapy remains the golden standard for unresectable or metastatic GC, both in the first and second-line settings, even if leading to a fair outcome improvement.: In recent years, according to the concept of 'precision medicine', new potential molecular targets have been examined. We provided a general outline of the current first- and second-line chemotherapies. New therapeutic possibilities are also reviewed, particularly HER2, EGFR, VEGF, TKI, MEK and BRAF inhibitors, and immunotherapy. Furthermore, published clinical trials are utilized to analyze the principal drug effectiveness in GC.: GC is characterized by vast cancer heterogeneity and individual's efficacy to different drugs. The ongoing trials have the potentiality of reshaping the landscape of systemic treatments for GC in the very next years. Nowadays, amongst therapeutic combinations, the addition of ICIs to chemotherapy has yielded encouraging results needing confirmation. In the next future, systematic implementation of gene profiling and further explorations of combination therapies will likely change the treatment scenario.

摘要

胆囊癌(GC)是一种罕见的恶性肿瘤,预后不良。如果早期诊断并及时手术切除,可能会被治愈。不幸的是,尽管手术切除率很高,但只有少数 GC 患者可以进行手术。对于不可切除或转移性 GC,传统化疗仍然是一线和二线治疗的金标准,即使这只能带来一定程度的疗效改善。近年来,根据“精准医学”的概念,已经研究了新的潜在分子靶点。我们概述了目前一线和二线化疗的情况。还回顾了新的治疗可能性,特别是 HER2、EGFR、VEGF、TKI、MEK 和 BRAF 抑制剂以及免疫疗法。此外,还利用已发表的临床试验分析了 GC 中主要药物的疗效。GC 具有广泛的肿瘤异质性和个体对不同药物的疗效差异。正在进行的试验有可能在未来几年重塑 GC 的系统治疗格局。如今,在各种治疗组合中,将免疫检查点抑制剂(ICIs)与化疗联合使用已经取得了令人鼓舞的结果,需要进一步证实。在未来,系统地实施基因谱分析并进一步探索联合治疗可能会改变治疗方案。

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