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针对非小细胞肺癌的靶向治疗——最新进展与未来展望。

Targeted therapies for treatment of non-small cell lung cancer--Recent advances and future perspectives.

机构信息

European Institute of Cancer Research (EICR), Carrer Del Passeig, 2, Terrassa, 08221, Spain.

Institute of Pharmacology and Preventive Medicine (IPPMED), Bahnhofstr. 20, Cloppenburg, 49661, Germany.

出版信息

Int J Cancer. 2016 Jun 1;138(11):2549-61. doi: 10.1002/ijc.29915. Epub 2015 Dec 15.

Abstract

Non-small cell lung cancer (NSCLC) is one of the most deadly cancers worldwide, with poor prognosis once the disease has progressed past the point at which surgery is a viable option. Whilst chemotherapy has improved survival over recent decades, there is still great need for improvements in treatments for patients with advanced disease. Over the last decade, a variety of such drugs have received market approval for treating NSCLC, with a variety of others in the pipeline. Here, we review the development of targeted therapies for the treatment of advanced or metastatic NSCLC, including those already in clinical practice and those in early trials. The epidermal growth factor receptor (EGFR) inhibitors, gefitinib, erlotinib and afatinib; the anaplastic lymphoma kinase (ALK) inhibitor, crizotinib; and the anti-vascular endothelial growth factor receptor monoclonal antibody, bevacizumab, are already providing improved survival for patients with NSCLC. Moreover, the discovery of EGFR mutations and ALK rearrangements has enabled the identification of patients who are more likely to benefit from a specific drug. The recent approval of the immune checkpoint inhibitor nivolumab, along with the designation of alectinib and MPDL3280A as breakthrough therapies by the FDA, demonstrates how rapidly this area of research is expanding. Over the last decade there has been significant progress made in the treatment of advanced NSCLC, and the large and varied selection of drugs currently undergoing trials provide great promise for improving the prognosis of this highly prevalent and deadly form of cancer.

摘要

非小细胞肺癌(NSCLC)是全球最致命的癌症之一,一旦疾病发展到手术可行的阶段,预后就很差。虽然化疗在最近几十年提高了生存率,但仍迫切需要改进晚期疾病患者的治疗方法。在过去的十年中,已有多种此类药物获得市场批准用于治疗 NSCLC,还有许多其他药物正在研发中。在这里,我们回顾了用于治疗晚期或转移性 NSCLC 的靶向治疗药物的发展,包括已在临床实践中的药物和处于早期试验阶段的药物。表皮生长因子受体(EGFR)抑制剂吉非替尼、厄洛替尼和阿法替尼;间变性淋巴瘤激酶(ALK)抑制剂克唑替尼;以及抗血管内皮生长因子受体单克隆抗体贝伐珠单抗,已经为 NSCLC 患者提供了更长的生存时间。此外,EGFR 突变和 ALK 重排的发现使我们能够确定更有可能从特定药物中受益的患者。免疫检查点抑制剂 nivolumab 的最近批准,以及 FDA 将 alectinib 和 MPDL3280A 指定为突破性疗法,表明该研究领域的发展速度之快。在过去的十年中,晚期 NSCLC 的治疗取得了重大进展,目前正在进行临床试验的大量不同药物为改善这种高度流行和致命形式的癌症的预后提供了巨大希望。

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