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非小细胞肺癌中的BRAF突变:雅努斯终于把门打开了吗?

BRAF mutations in non-small cell lung cancer: has finally Janus opened the door?

作者信息

Caparica Rafael, de Castro Gilberto, Gil-Bazo Ignacio, Caglevic Christian, Calogero Raffaele, Giallombardo Marco, Santos Edgardo S, Raez Luis E, Rolfo Christian

机构信息

Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da USP, São Paulo, Brazil.

Oncology Department, Clínica Universidad de Navarra, Center for Applied Medical Research (CIMA), Pamplona, Spain.

出版信息

Crit Rev Oncol Hematol. 2016 May;101:32-9. doi: 10.1016/j.critrevonc.2016.02.012. Epub 2016 Feb 27.

Abstract

B-Raf mutations occur in about 1-2% of non-small cell lung cancers (NSCLC). These mutations generate a permanent activation of the mitogen activated protein kinase (MAPK) pathway, which promotes tumor growth and proliferation. In the present review, we discuss B-Raf mutation epidemiology, diagnostic methods to detect B-Raf mutations, the role of B-Raf as a driver mutation and a potential therapeutic target in NSCLC. The results of clinical trials involving B-Raf or MAPK pathway inhibitors for the treatment of NSCLC are also discussed. Clinical trials evaluating B-Raf inhibitors in BRAF mutated NSCLC patients have shown promising results, and larger prospective studies are warranted to validate these findings. Enrollment of these patients in clinical trials is an interesting strategy to offer a potentially more effective and less toxic targeted therapy.

摘要

B-Raf突变发生在约1%-2%的非小细胞肺癌(NSCLC)中。这些突变会导致丝裂原活化蛋白激酶(MAPK)通路的永久激活,从而促进肿瘤生长和增殖。在本综述中,我们讨论了B-Raf突变的流行病学、检测B-Raf突变的诊断方法、B-Raf作为驱动突变以及NSCLC潜在治疗靶点的作用。还讨论了涉及B-Raf或MAPK通路抑制剂治疗NSCLC的临床试验结果。评估B-Raf抑制剂用于BRAF突变NSCLC患者的临床试验已显示出有前景的结果,有必要开展更大规模的前瞻性研究来验证这些发现。将这些患者纳入临床试验是一种提供潜在更有效且毒性更小的靶向治疗的有趣策略。

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