Although the last two decades have seen a broad improvement in overall survival, colorectal cancer is still the second leading cause of cancer deaths worldwide. Patient populations continue to face poor disease prognoses due to the challenges of early detection and the molecular subtypes driving their colorectal cancer. Consequently, many patients present with metastatic colorectal cancer, which often limits options and shifts treatment focus away from curative interventions. BRAFV600E mutations are present in approximately 10% of colorectal cancer tumors and are associated with uninhibited cell proliferation, reduced apoptosis, and resistance to standard therapeutic options. In colorectal cancer, BRAFV600E mutations are associated with decreased overall survival, poor treatment responses, and different patterns of metastatic spread compared with tumors with wild-type BRAF . Success in treating other BRAFV600E -mutant cancers with BRAF inhibitors as monotherapy has not translated into efficacious treatment of metastatic colorectal cancer. Consequently, combination therapy with inhibitors of BRAF, MEK, and EGFR, which overcomes the innate treatment-resistant characteristics of BRAF V600E-mutant colorectal cancer, is now recommended by treatment guidelines.

中文翻译：

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BRAFV600E 突变转移性结直肠癌临床结果的改善。

尽管过去二十年的总体生存率有了广泛的提高，但结直肠癌仍然是全球癌症死亡的第二大原因。由于早期检测的挑战和导致结直肠癌的分子亚型，患者群体继续面临着不良的疾病预后。因此，许多患者出现转移性结直肠癌，这通常会限制选择并将治疗重点从治愈性干预转移。BRAFV600E 突变存在于大约 10% 的结直肠癌肿瘤中，并且与不受抑制的细胞增殖、细胞凋亡减少和对标准治疗方案的抗性有关。在结直肠癌中，BRAFV600E 突变与总体生存率降低、治疗反应差、与野生型 BRAF 肿瘤相比，转移扩散的不同模式。使用 BRAF 抑制剂作为单一疗法成功治疗其他 BRAFV600E 突变癌症并没有转化为转移性结直肠癌的有效治疗。因此，治疗指南现在推荐与 BRAF、MEK 和 EGFR 抑制剂联合治疗，以克服 BRAF V600E 突变型结直肠癌的先天抗药性特征。