抗egfr抗体联合治疗扩展RAS/ BRAF野生型转移性结直肠癌

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Pharmacogenomics Pub Date : 2025-01-01 Epub Date: 2025-03-17 DOI:10.1080/14622416.2025.2479414
Ioannis A Voutsadakis
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引用次数: 0

摘要

受体酪氨酸激酶途径在癌症中经常被解除调控。用小分子抑制剂或单克隆抗体抑制这些途径已成为肿瘤学治疗手段的重要补充。自从引入靶向受体酪氨酸激酶途径的药物以来,很明显并非所有患者都对治疗有反应。因此,人们一直在寻找生物标志物来预测针对酪氨酸激酶的药物的反应和益处。表皮生长因子受体(EGFR)是表皮生长因子受体家族的四种受体之一,靶向EGFR的单克隆抗体是最早用于实体瘤的靶向治疗之一。这类药物中的两种,西妥昔单抗和帕尼单抗,最初用于转移性结直肠癌患者,不需要任何生物标志物。很快,人们就清楚地看到,这些反应大多发生在没有KRAS癌基因突变的患者身上。目前,该通路的其他突变,包括KRAS的非外显子2突变、同源GTPase NRAS、激酶BRAF和PIK3CA等通路蛋白的突变,已被添加到对西妥昔单抗和帕尼单抗的反应性预测评估中。在这篇综述中,抗egfr单克隆抗体抑制剂在转移性结直肠癌中无扩展RAS和BRAF突变的预测性生物标志物景观将被检查。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Treatment of extended RAS/BRAF wild-type metastatic colorectal cancer with anti-EGFR antibody combinations.

Receptor tyrosine kinase pathways are frequently deregulated in cancer. Inhibiting these pathways with small molecule inhibitors or monoclonal antibodies has become a crucial addition to the therapeutic armamentarium in oncology. Since the introduction of drugs that target receptor tyrosine kinase pathways, it has become evident that not all patients respond to treatment. Therefore, biomarkers to predict response and benefit of drugs targeting tyrosine kinases have been sought. Monoclonal antibodies targeting the Epidermal Growth Factor Receptor (EGFR), one of the four receptors of the EGFR family were among the first targeted therapies used in solid tumors. Two drugs of this class, cetuximab and panitumumab, have been used in patients with metastatic colorectal cancer initially without any biomarker requirement. Soon, it became clear that responses were mostly observed in patients without mutations in KRAS oncogene. Currently, additional mutations of the pathway, including non-exon 2 mutations in KRAS, mutations in the homologous GTPase NRAS, in kinase BRAF and PIK3CA and other pathway proteins, have been added in the evaluation for responsiveness prediction to cetuximab and panitumumab. In this review, the predictive biomarker landscape for anti-EGFR monoclonal antibody inhibitors in metastatic colorectal cancers with no extended RAS and BRAF mutations will be examined.

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来源期刊
Pharmacogenomics
Pharmacogenomics 医学-药学
CiteScore
3.40
自引率
9.50%
发文量
88
审稿时长
4-8 weeks
期刊介绍: Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.
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