Orlandi Armando, Calegari Alessandra, Inno Alessandro, Berenato Rosa, Caporale Marta, Niger Monica, Bossi Ilaria, Di Bartolomeo Maria, de Braud Filippo, Pietrantonio Filippo
Medical Oncology Department, Università Cattolica del Sacro Cuore, Rome, Italy.
Medical Oncology, Sacro Cuore Don Calabria Hospital, Negrar - Verona, Italy.
Pharmacogenomics. 2015 Dec;16(18):2069-81. doi: 10.2217/pgs.15.140. Epub 2015 Nov 30.
BRAF mutations are detectable in about 5-15% of metastatic colorectal cancer (mCRC) patients and represent a clear negative prognostic factor. While in BRAF-mutated (BRAFmt) metastatic melanoma TKI target therapies (BRAF and MEK inhibitor), both alone or in combination, have shown significant efficacy, in BRAFmt CRC single-agent BRAF-inhibitors as well as chemotherapy seem to be ineffective. The critical role of EGFR in CRC and its multiple downstreaming pathways seem to be involved in this lack of response. In recent years, preclinical investigations and retrospective studies slowly increased our knowledge on BRAFmt CRC. This review analyses preclinical data and discusses several clinical trials in order to explore new therapeutic strategies targeting BRAFmt mCRC.
在约5%-15%的转移性结直肠癌（mCRC）患者中可检测到BRAF突变，其是一个明确的不良预后因素。在BRAF突变（BRAFmt）的转移性黑色素瘤中，TKI靶向治疗（BRAF和MEK抑制剂），无论是单独使用还是联合使用，都已显示出显著疗效，但在BRAFmt结直肠癌中，单药BRAF抑制剂以及化疗似乎均无效。表皮生长因子受体（EGFR）在结直肠癌及其多个下游通路中的关键作用似乎与这种无反应有关。近年来，临床前研究和回顾性研究逐渐增加了我们对BRAFmt结直肠癌的认识。本综述分析了临床前数据并讨论了几项临床试验，以探索针对BRAFmt mCRC的新治疗策略。
