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Cetuximab for treating non-small cell lung cancer

机译:西蒂索昔单抗治疗非小细胞肺癌

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Introduction: Epidermal Growth Factor Receptor (EGFR)-dependent signaling plays a crucial role in epithelial cancer biology, and dictated the development of several targeting agents. The mouse-human chimeric antibody Cetuximab was among the first to be developed. After about two decades of clinical research it has gained a significant place in the management of advanced colorectal and head and neck cancers, whereas its development in non small cell lung cancer (NSCLC) has not led to a place in routine clinical practice, because of marginal clinical benefit despite statistically significant Phase III trials. Recent data from ongoing trials suggest that more careful selection based on molecular markers may identify good responders. Areas covered: In this article, the authors review the literature concerning basic science studies identifying EGFR as a therapeutic target, pharmacological development of Cetuximab, its pharmacodynamics and pharmacokinetics, and clinical trials on Cetuximab in NSCLC, focusing on recent findings on putative predictive biomarkers. Expert opinion: Cetuximab currently has no role in NSCLC treatment outside of research settings. We argue that failure to identify a predictive biomarker early on has hampered its chances to enter routine practice. Although recent research suggests benefit in highly selected patient subsets, its potential impact is severely dampened by lack of regulatory body approval and the emergence of competitors for the same niches.
机译:简介:表皮生长因子受体(EGFR) - 依赖信号传导在上皮癌生物学中起着至关重要的作用,并决定了几种靶向剂的发育。小鼠 - 人嵌合抗体己酮嗪是首次开发的。经过大约二十年的临床研究,它在治疗晚期结直肠头和颈部癌症中获得了显着的位置,而其在非小细胞肺癌(NSCLC)的发育并未导致常规临床实践中的一个地方,因为尽管存在统计学显着的III期试验,但边际临床效益。正在进行的试验中的最近数据表明,基于分子标记的更加仔细选择可以识别良好的响应者。提出的领域:本文审查了关于鉴定EGFR作为治疗目标的基础科学研究的文献,作​​为治疗目标,其药效学和药代动力学的药理发育,以及在NSCLC中的西妥昔单抗的临床试验,重点是推定预测生物标志物的最近发现。专家意见:Cetuximab目前在研究设置之外的NSCLC处理中没有任何作用。我们认为未能识别预测生物​​标志物,这阻碍了其进入常规实践的机会。尽管最近的研究表明,在高度选择的患者亚集中有益,但其潜在的影响因缺乏监管机构批准和同一利基的竞争对手的出现而严重抑制。

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