Amplification of the MET receptor to drive resistance to anti-EGFR therapies in colorectal cancer.
Amplification of the MET receptor to drive resistance to anti-EGFR therapies in colorectal cancer.
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MET 受体的扩增可驱动结直肠癌中抗 EGFR 疗法的耐药性。
DOI：
10.1200/jco.2013.31.15_suppl.11005
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发表时间：
2013
影响因子：
45.3
通讯作者：
S. Siena
中科院分区：
文献类型：
--
作者：
A. Bardelli;S. Corso;A. Bertotti;S. Hobor;G. Siravegna;A. Sartore;Giorgia Migliardi;F. Galimi;C. Lauricella;C. Zanon;A. Amatu;M. Gambacorta;L. Diaz;V. Velculescu;M. Sausen;P. Comoglio;L. Trusolino;F. Nicolantonio;S. Giordano;S. Siena
11005背景：抗EGFR单克隆抗体西妥昔单抗和帕尼单抗用于治疗转移性结直肠癌患者，但其临床疗效受到获得性耐药性发展的限制。我们最近报道，继发性KRAS突变是导致大约50%最初对西妥昔单抗或帕尼单抗有反应的患者获得性耐药的原因（Misale et al.，Nature 2012;迪亚兹等人，Nature 2012）。在这里，我们研究了在抗EGFR治疗过程中未发生KRAS突变的CRC患者复发的分子基础。研究方法：将下一代测序应用于肿瘤活检，以确定与mCRC患者中西妥昔单抗和帕尼单抗复发相关的遗传改变。循环肿瘤DNA中遗传改变的检测和定量用于监测血液样品中KRAS突变和MET扩增的发生。结果：来自未发生KRAS突变的患者的肿瘤活检的分子分析…
11005 Background: The anti EGFR monoclonal antibodies cetuximab and panitumumab are used to treat metastatic colorectal cancer patients but their clinical efficacy is limited by the development of acquired resistance. We recently reported that secondary KRAS mutations are responsible for acquired resistance in approximately 50% of the patients who initially respond to cetuximab or panitumumab (Misale et al., Nature 2012; Diaz et al., Nature 2012). Here we studied the molecular bases of relapse in CRC patients who do not develop KRAS mutations during the course of anti-EGFR therapy. Methods: Next generation sequencing was applied to tumor biopsies to identify genetic alterations associated with relapse to cetuximab and panitumumab in mCRC patients. Detection and quantitation of genetic alterations in circulating tumor DNA was used to monitor the occurrence of KRAS mutations and MET amplification in blood samples. Results: Molecular analyses of tumor biopsies from patients who did not develop KRAS mutations...