Exploring the best treatment options for BRAF-mutant metastatic colon cancer.,British Journal of Cancer

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Exploring the best treatment options for BRAF-mutant metastatic colon cancer.
British Journal of Cancer ( IF 6.4 ) Pub Date : 2019-07-29 , DOI: 10.1038/s41416-019-0526-2
Julien Taieb _{1,

2} , Alexandra Lapeyre-Prost ₁ , Pierre Laurent Puig _{2,

3} , Aziz Zaanan _{1,

2}

Affiliation

The BRAFV600E mutation is a well-accepted poor prognostic factor in patients with metastatic colorectal cancer (mCRC), as it confers Ras-independent stimulation of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway involved in proliferation, migration, angiogenesis and the suppression of apoptosis. Analysis of the potential predictive value of BRAF for treatment efficacy is inherently confounded by this known prognostic impact. Currently, approved therapeutic strategies for patients with BRAF-mutant (BRAF-mt) mCRC are suboptimal, and uncertainty exists regarding how to best treat these patients. Based on the available evidence, it is currently not possible to confirm the superiority of any available treatment options cited in European Society for Medical Oncology and National Comprehensive Cancer Network guidelines (that is, doublet or triplet chemotherapy regimens plus anti-vascular endothelial growth factor or anti-epidermal growth factor receptors), even if triplet chemotherapy plus bevacizumab is the most accepted standard regimen. In this review, we highlight still-emerging strategies that could be deployed to combat BRAF-mt mCRC, including triplet chemotherapy plus available biologic agents, rationally derived combinations of targeted agents and immunotherapy. While it is clear that the needs of patients with BRAF-mt mCRC are currently unmet, we are cautiously optimistic that the recently renewed research interest in these patients will yield clinically relevant insights and therapeutic strategies.

中文翻译：

探索 BRAF 突变转移性结肠癌的最佳治疗方案。

BRAFV600E 突变是转移性结直肠癌 (mCRC) 患者公认的不良预后因素，因为它赋予细胞外信号调节激酶/丝裂原激活蛋白激酶途径的 Ras 独立刺激，参与增殖、迁移、血管生成和抑制细胞凋亡。BRAF 对治疗效果的潜在预测价值的分析本质上与这种已知的预后影响相混淆。目前，批准的针对 BRAF 突变（BRAF-mt）转移性结直肠癌患者的治疗策略并不理想，并且如何最好地治疗这些患者存在不确定性。根据现有证据，目前无法确认欧洲肿瘤内科学会和国家综合癌症网络指南中引用的任何可用治疗方案（即双联或三联化疗方案加抗血管内皮生长因子或抗表皮生长因子受体），即使三联化疗加贝伐单抗是最被接受的标准方案。在这篇综述中，我们重点介绍了可用于对抗 BRAF-mt mCRC 的新兴策略，包括三联化疗加可用的生物制剂、合理衍生的靶向药物和免疫疗法的组合。虽然目前 BRAF-mt mCRC 患者的需求显然尚未得到满足，但我们谨慎乐观地认为，最近对这些患者重新产生的研究兴趣将产生临床相关的见解和治疗策略。

更新日期：2019-07-29

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