Colorectal cancer (CRC) remains one of the main causes of cancer mortality around the world. Although global mortality is decreasing, an increased mortality in young adults (<50 years old) has been reported.¹ Virus-induced rapidly accelerated fibrosarcoma (v-RAF) was first identified as an oncogene through the cloning of a viral mouse gene that had the ability to transform NIH3T3 cells. Its human ortholog CRAF (RAF-1) and subsequently the related kinase genes ARAF and BRAF were later found to be commonly mutated in cancer. This RAF kinase family consists of key components of the RAS–RAF–MEK–ERK signaling cascade (MAPK pathway; Figures 1 and 2). The BRAF (v-RAF murine sarcoma viral oncogene homolog B; B-type raf kinase) gene is located on chromosome 7. Like RAS, the serine/threonine-protein kinase BRAF is a downstream signaling protein in the epidermal growth factor receptor (EGFR)-mediated pathway; in vitro experiences have highlighted that some genes are differently expressed in BRAF-mutant and wild-type CRC cell lines.^2,3 A characteristic gene expression signature associated with BRAF mutation has been identified.⁴ However, attempts to directly inhibit the active BRAF protein failed in metastatic CRC (mCRC),⁵ suggesting a more complex (or at least different) carcinogenic process in this disease. Nevertheless, BRAF mutation testing is now recommended for mCRC in the latest National Comprehensive Cancer Network guidelines.⁶ We will discuss and review here the more recent literature that specifically concerns BRAF-mutant CRC.

中文翻译：

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BRAF突变型结直肠癌的分子靶向治疗

大肠癌（CRC）仍然是全球癌症死亡的主要原因之一。尽管全球死亡率正在下降，但据报告，年轻人（<50岁）的死亡率有所增加。¹通过克隆具有转化NIH3T3细胞能力的病毒小鼠基因，病毒诱导的快速加速纤维肉瘤（v-RAF）首先被鉴定为癌基因。后来发现其人类直系同源CRAF（RAF-1）以及相关的激酶基因ARAF和BRAF在癌症中普遍发生突变。该RAF激酶家族由RAS–RAF–MEK–ERK信号级联反应（MAPK途径；图1和2）。的BRAF（V-RAF鼠肉瘤病毒癌基因同源物B; B型Raf激酶）基因位于染色体7一样RAS，丝氨酸/苏氨酸-蛋白激酶BRAF是在表皮生长因子受体的下游信号转导蛋白（EGFR ）介导的途径; 体外经验表明，某些基因在BRAF突变和野生型CRC细胞系中表达不同。^2,3已经确定了与BRAF突变相关的特征性基因表达特征。⁴但是，直接抑制活性BRAF蛋白的尝试在转移性CRC（mCRC）中失败了，⁵提示该疾病的致癌过程更为复杂（或至少不同）。尽管如此，现在在最新的《国家综合癌症网络指南》中仍建议对mCRC进行BRAF突变测试。^[6]我们将在这里讨论和审查专门涉及BRAF突变CRC的最新文献。