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新型抗癌药物——从细胞毒性全身化疗到基于靶点的药物

[New anti-cancer agents--from cytotoxic systemic chemotherapy to target-based agents].

作者信息

Yokoba Masanori, Yanase Nobuo, Masuda Noriyuki

机构信息

Dept. of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Japan.

出版信息

Gan To Kagaku Ryoho. 2005 Jun;32(6):783-8.

Abstract

Lung cancer is the leading cause of cancer-related death throughout the world including Japan. During the 1990s, new cytotoxic agents such as irinotecan, paclitaxel, docetaxel, vinorelbine, gemcitabine, and amrubicin showed impressive single-agent activity in patients with lung cancer. To date, clinical research has defined the current standard chemotherapy for advanced non-small cell lung cancer (NSCLC) as modern platinum-based doublets considered more efficacious than any single regimen and with no added benefit to triplet therapies. However, we have reached an efficacy plateau with these agents. Rearrangement of the drug combination or change of the drug doses and schedules will not result in significant further progress. New, less toxic agents that improve survival and quality of life are clearly needed. In the last three decades, we have gained a growing understanding of the molecular biologic changes and the complex series of cellular signals that allow cancer cells to manifest behavior. This provides an opportunity to develop novel therapies aimed at inhibiting some of these changes and signals. Targeted agents, primarily the epidermal growth factor receptor inhibitors, have led to a new era in the treatment of NSCLC. This paper will review the current status of cytotoxic agents and molecular targeted therapy in lung cancer potential useful in the treatment of the patients.

摘要

肺癌是包括日本在内的全球癌症相关死亡的主要原因。在20世纪90年代,伊立替康、紫杉醇、多西他赛、长春瑞滨、吉西他滨和氨柔比星等新型细胞毒性药物在肺癌患者中显示出令人印象深刻的单药活性。迄今为止,临床研究已将晚期非小细胞肺癌(NSCLC)的当前标准化疗定义为现代铂类双联疗法,该疗法被认为比任何单一方案更有效,且三联疗法没有额外益处。然而,我们使用这些药物已达到疗效平台期。重新组合药物或改变药物剂量及给药方案不会带来显著的进一步进展。显然需要新的、毒性较小且能提高生存率和生活质量的药物。在过去三十年中,我们对分子生物学变化以及使癌细胞表现出特定行为的一系列复杂细胞信号有了越来越深入的了解。这为开发旨在抑制其中一些变化和信号的新型疗法提供了机会。靶向药物,主要是表皮生长因子受体抑制剂,引领了NSCLC治疗的新时代。本文将综述细胞毒性药物和分子靶向治疗在肺癌治疗中对患者可能有用的当前状况。

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