KRAS 突变与转移性结直肠癌对抗 EGFR 单克隆抗体的敏感性：一个未解决的问题。
KRAS mutations and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal carcinoma: an open issue.
机构信息
Scientific Institute for Research and Treatment of Cancer Giovanni Paolo II, Medical and Experimental Oncology Unit, Bari, Italy.
出版信息
Expert Opin Biol Ther. 2009 May;9(5):565-77. doi: 10.1517/14712590902870394.
BACKGROUND
Cetuximab and panitumumab, mAbs targeting EGFR, are registered for metastatic colorectal carcinoma (mCRC) patients whose tumors express EGFR as determined by immunohistochemistry. However, this method is not predictive of treatment efficacy. KRAS, the human homolog of the Kirsten rat sarcoma-2 virus oncogene, encodes a small G-protein that functions downstream of EGFR-induced signalling.
OBJECTIVE/METHODS: To examine KRAS mutations as predictive factors of response to anti-EGFR mAbs using recently published data.
RESULTS/CONCLUSIONS: Several retrospective studies show that efficacy of these mAbs is confined to patients with wild type KRAS and genotyping of tumors should be considered before treatment. The absence of KRAS mutations does not guarantee an improved likelihood of response to cetuximab and panitumumab. Investigation of other genetic and epigenetic biomarkers will be useful to further refine the responder population. Prospective studies to test the efficacy of combined therapies simultaneously targeting EGFR and the RAS/RAF/MAPK signalling pathways for mCRC are warranted.
背景
西妥昔单抗和帕尼单抗是针对表皮生长因子受体（EGFR）的单克隆抗体，已被注册用于其肿瘤组织中通过免疫组织化学法检测到 EGFR 表达的转移性结直肠癌（mCRC）患者。然而，这种方法并不能预测治疗效果。KRAS 是人类 EGFR 诱导信号下游的小 G 蛋白，是 Kirsten 鼠肉瘤病毒 2 癌基因的人类同源物。
目的/方法：利用最近发表的数据，研究 KRAS 突变作为抗 EGFR 单克隆抗体反应预测因子的作用。
结果/结论：几项回顾性研究表明，这些单克隆抗体的疗效仅限于 KRAS 野生型患者，在治疗前应考虑对肿瘤进行基因分型。KRAS 突变的缺失并不能保证西妥昔单抗和帕尼单抗治疗应答率的提高。研究其他遗传和表观遗传生物标志物将有助于进一步细化应答人群。有必要进行前瞻性研究，以测试同时针对 EGFR 和 RAS/RAF/MAPK 信号通路的联合治疗方案在 mCRC 中的疗效。
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