Morris Van K, Bekaii-Saab Tanios
University of Texas MD Anderson Cancer Center, Houston, Texas.
Mayo Clinic College of Medicine and Science, Phoenix, Arizona.
Clin Cancer Res. 2020 Sep 1;26(17):4435-4441. doi: 10.1158/1078-0432.CCR-19-3809. Epub 2020 Apr 6.
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. 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, mutations are associated with decreased overall survival, poor treatment responses, and different patterns of metastatic spread compared with tumors with wild-type Success in treating other -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 -mutant colorectal cancer, is now recommended by treatment guidelines.
尽管在过去二十年中总体生存率有了广泛提高,但结直肠癌仍是全球癌症死亡的第二大主要原因。由于早期检测面临挑战以及驱动结直肠癌的分子亚型,患者群体仍然面临较差的疾病预后。因此,许多患者表现为转移性结直肠癌,这通常会限制治疗选择,并将治疗重点从根治性干预措施转移开。约10%的结直肠癌肿瘤存在 BRAF 突变,这些突变与不受抑制的细胞增殖、细胞凋亡减少以及对标准治疗方案的耐药性相关。在结直肠癌中,与野生型 BRAF 的肿瘤相比,BRAF 突变与总体生存率降低、治疗反应不佳以及不同的转移扩散模式相关。用 BRAF 抑制剂作为单一疗法治疗其他 BRAF 突变癌症的成功经验并未转化为转移性结直肠癌的有效治疗方法。因此,治疗指南现在推荐 BRAF、MEK 和 EGFR 抑制剂联合治疗,以克服 BRAF 突变型结直肠癌固有的治疗耐药特性。