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转移性肾细胞癌的当前和新兴治疗靶点。

Current and Emerging Therapeutic Targets for Metastatic Renal Cell Carcinoma.

机构信息

Department of Medicine, Stony Brook University Hospital, Stony Brook, NY, USA.

Division of Hematology/Oncology, Department of Medicine, Northport VA Medical Center, Northport, NY, USA.

出版信息

Curr Oncol Rep. 2018 Apr 2;20(5):41. doi: 10.1007/s11912-018-0684-z.

Abstract

PURPOSE OF REVIEW

The treatment of advanced renal cell carcinoma has evolved dramatically over recent years. In this review, we will summarize current and emerging therapies based on molecular targets and provide insight into treatment strategy for metastatic renal cell carcinoma.

RECENT FINDINGS

We have witnessed a paradigm shift in the therapeutic landscape as treatment was formerly reliant on cytokine-based agents which have now been replaced with therapies targeting angiogenesis, mammalian target of rapamycin pathways, and immune responses. These dramatic changes are primarily due to our improved understanding of the underlying mutations and molecular mechanisms leading to tumorigenesis and progression. We now have targeted agents in the form of small-molecule tyrosine kinase inhibitors, monoclonal antibodies, and mTOR inhibitors. Moreover, immunotherapy-targeting checkpoints of T-lymphocyte activity has provided increased overall survival and a new class of agents with potential to radically change the treatment options. With these agents and their combination, durable responses are increasingly seen even though treatment resistance remains a huge challenge. New treatment strategies are rapidly developing and the therapeutic landscape is expected for further evolution.

摘要

目的综述

近年来,晚期肾细胞癌的治疗发生了巨大变化。在这篇综述中,我们将根据分子靶点总结目前和新出现的治疗方法,并深入探讨转移性肾细胞癌的治疗策略。

最近的发现

治疗方法发生了重大转变,以前依赖细胞因子为基础的药物,现在已被针对血管生成、哺乳动物雷帕霉素靶蛋白途径和免疫反应的治疗方法所取代。这些巨大的变化主要是由于我们对导致肿瘤发生和进展的潜在突变和分子机制有了更好的理解。我们现在有了以小分子酪氨酸激酶抑制剂、单克隆抗体和 mTOR 抑制剂为形式的靶向药物。此外,针对 T 淋巴细胞活性的免疫检查点的免疫疗法提供了更高的总生存率和一类有潜力从根本上改变治疗选择的新药物。这些药物及其组合的应用,即使治疗耐药性仍然是一个巨大的挑战,也越来越能看到持久的反应。新的治疗策略正在迅速发展,治疗领域预计将进一步发展。

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