New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: do all roads lead to RAS?
New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: do all roads lead to RAS?
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DOI：
10.18632/oncotarget.4959
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发表时间：
2015-09-22
期刊：
影响因子：
--
通讯作者：
Russo A
中科院分区：
文献类型：
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作者：
Bronte G;Silvestris N;Castiglia M;Galvano A;Passiglia F;Sortino G;Cicero G;Rolfo C;Peeters M;Bazan V;Fanale D;Giordano A;Russo A
西妥昔单抗和帕尼图单抗联合抗表皮生长因子受体治疗是转移性结直肠癌的主要靶向治疗和标准化疗相结合。许多临床研究表明，对于没有EGFR途径突变的患者来说，添加这些药物是有好处的。许多生物标志物，包括KRAS和NRAS突变，BRAF突变，PIK3CA突变，PTEN缺失，AREG和Ereg表达，以及HER-2扩增，已经被确定为选择抗EGFR药物的应答者。在这些突变中，KRAS和NRAS突变目前被认为是预测原发耐药的最好因素。液体活检有助于分离循环中的肿瘤DNA，是研究抗EGFR单抗的原发和获得性耐药性的一种创新方法。然而，应该使用高灵敏度技术来识别与抗药性相关的广泛的基因突变。
Anti-epidermal growth factor receptor therapy with the monoclonal antibodies cetuximab and panitumumab is the main targeted treatment to combine with standard chemotherapy for metastatic colorectal cancer. Many clinical studies have shown the benefit of the addition of these agents for patients without mutations in the EGFR pathway. Many biomarkers, including KRAS and NRAS mutations, BRAF mutations, PIK3CA mutations, PTEN loss, AREG and EREG expression, and HER-2 amplification have already been identified to select responders to anti-EGFR agents. Among these alterations KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance. Liquid biopsy, which helps to isolate circulating tumor DNA, is an innovative method to study both primary and acquired resistance to anti-EGFR monoclonal antibodies. However, high-sensitivity techniques should be used to enable the identification of a wide set of gene mutations related to resistance.