Clinical Translational Research Division, The Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
Sci Signal. 2012 Oct 16;5(246):pe46. doi: 10.1126/scisignal.2003354.
The BRAF inhibitor vemurafenib has become an important treatment option for melanoma patients, the majority of whom have a BRAF(V600E) mutation driving their malignancy. However, this same agent does not generally benefit colon cancer patients who have the BRAF(V600E) mutation. Recent work suggests that BRAF(V600E) inhibition by vemurafenib results in decreased negative feedback to the epidermal growth factor receptor (EGFR) pathway and that the different clinical responses are due to differences in the amount of EGFR present in these two cancers. The experimental work that identified the feedback signaling was an elegant mix of functional genomic approaches and focused, hypothesis-driven cellular and molecular biology. The results of these studies suggest that combined treatment of BRAF(V600E)-driven colon cancers with both vemurafenib and EGFR inhibitors is worth clinical evaluation.
BRAF 抑制剂 vemurafenib 已成为黑色素瘤患者的重要治疗选择，大多数此类患者的恶性肿瘤由 BRAF(V600E)突变驱动。然而，这种药物通常对携带 BRAF(V600E)突变的结肠癌患者无效。最近的研究表明，vemurafenib 抑制 BRAF(V600E)会导致对表皮生长因子受体 (EGFR)途径的负反馈减少，而不同的临床反应则是由于这两种癌症中 EGFR 的数量存在差异所致。确定反馈信号的实验工作是功能基因组方法和聚焦、假设驱动的细胞和分子生物学的巧妙结合。这些研究的结果表明，用 vemurafenib 和 EGFR 抑制剂联合治疗 BRAF(V600E)驱动的结肠癌值得临床评估。
