Sorbonne Paris-Cité, Paris Descartes University, Assistance Publique Hôpitaux de Paris (APHP), Gastro-enterology and GI Oncology Department, Georges Pompidou European Hospital, Paris, France.
INSERM UMR-S1138, CNRS SNC5014, Paris Descartes University, Equipe labellisée Ligue Nationale contre le Cancer, Paris, France.
Br J Cancer. 2019 Sep;121(6):434-442. doi: 10.1038/s41416-019-0526-2. Epub 2019 Jul 29.
The BRAF 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.
BRAF 突变是转移性结直肠癌（mCRC）患者公认的预后不良因素，因为它会导致 Ras 独立的细胞外信号调节激酶/丝裂原活化蛋白激酶途径的刺激，该途径参与增殖、迁移、血管生成和抑制细胞凋亡。分析 BRAF 对治疗效果的潜在预测价值固有地受到这种已知预后影响的干扰。目前，BRAF 突变（BRAF-mt）mCRC 患者的批准治疗策略并不理想，对于如何最好地治疗这些患者存在不确定性。根据现有证据，目前尚无法证实欧洲肿瘤内科学会和国家综合癌症网络指南中提到的任何可用治疗选择的优越性（即双药或三药化疗方案加抗血管内皮生长因子或抗表皮生长因子受体），即使三药化疗加贝伐珠单抗是最被接受的标准方案。在这篇综述中，我们强调了仍在出现的策略，这些策略可以用来对抗 BRAF-mt mCRC，包括三药化疗加可用的生物制剂、靶向药物和免疫疗法的合理组合。虽然很明显，目前 BRAF-mt mCRC 患者的需求尚未得到满足，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。
