【摘要】 BRAF蛋白作为RAF蛋白家族中活性最强的蛋白激酶，主要通过促分裂素原活化蛋白激酶（mitogenactivated protein kinase,MAPK）/胞外信号调节激酶（extracellular signal-regulated kinase,ERK）信号通路调控细胞的增殖、分化与凋亡。在BRAF基因的所有突变类型中，Ⅰ类突变（V600突变）占比超过90%，其中V600E突变最为常见。BRAF^V600E突变导致大鼠肉瘤病毒癌基因同源物（rat sarcoma viral oncogene homolog,RAS）、RAF、MAPK/ERK激酶（MAPK/ERK kinase,MEK）、ERK信号通路失调，这些关键信号通路形成密集的交叉互作网络，共同驱动细胞异常增殖。BRAF^V600E突变与多种肿瘤的发生、发展相关，在黑色素瘤和甲状腺癌中发生率最高，在结直肠癌、非小细胞肺癌及胶质瘤中相对少见。目前，大量临床研究与试验已证实BRAF抑制剂和MEK抑制剂在BRAF^V600E突变型肿瘤治疗中的有效性。美国食品药物管理局（Food and Drug Administration,FDA）已批准达拉非尼联合曲美替尼用于治疗携带BRAF^V600E突变的不可切除或转移性实体瘤。这一疗法被批准虽然标志着BRAF突变型肿瘤治疗范式的转变，但仍面临不良反应及耐药性等问题，靶向治疗方案仍需进一步优化和探索。总结BRAF^V600E突变相关的分子机制及其在相关肿瘤中的最新研究进展，探讨其在肿瘤精准诊断和靶向治疗方案中的意义，有助于开发更安全有效的靶向治疗策略。更多还原

【Abstract】 BRAF protein is the most active protein kinase in the RAF protein family, and it mainly regulates cell proliferation, differentiation, and apoptosis through the mitogen-activated protein kinase（MAPK）/extracellular signal-regulated kinase（ERK） signaling pathway. Among all BRAF mutation types, class I mutations（V600 mutations） account for more than 90%, with V600E being the most common. The BRAF ^V600E mutation leads to dysregulation of rat sarcoma viral oncogene homolog（RAS）/RAF, MAPK/ERK kinase（MEK）/ERK signaling pathways, forming a dense cross-talk interaction network with multiple key signaling pathways, which together drive abnormal cell proliferation. BRAF ^V600E mutation is associated with the onset and progression of various tumors. It shows the highest mutation frequency in melanoma and thyroid cancer, but is relatively rare in colorectal cancer, nonsmall cell lung cancer, and glioma. Currently, a large number of clinical studies and trials have confirmed the efficacy of BRAF inhibitors and MEK inhibitors in the treatment of tumors with BRAF ^V600E mutations. The Food and Drug Administration（FDA） has approved dabrafenib combined with trametinib for unresectable or metastatic solid tumors carrying the BRAF ^V600E mutation. The approval of this therapy marks a transformation in the treatment paradigm for BRAF-mutated tumors, but challenges such as adverse reactions and drug resistance remain, and targeted therapy regimens still require further optimization and exploration. Summarizing the molecular mechanisms related to BRAF ^V600E mutation and reviewing the latest research progress in associated tumors is important for clarifying its significance in precise tumor diagnosis and targeted treatment. This may contribute to the development of safer and more effective targeted treatment strategies.更多还原