Since their discovery in 2002,BRAFmutations have been identified as clear drivers of oncogenesis in several cancer types. Currently, their incidence rate is nearly 7% of all solid tumors with BRAF V600E constituting approximately 90% of these diagnoses. In melanoma, thyroid cancer, and histiocytic neoplasms, BRAF hotspot mutations are found at a rate of about 50%, while in lung and colorectal cancers they range from 3% to 10% of reported cases. Though present in other malignancies such as breast and ovarian cancers, they constitute a small portion of diagnoses (<1%). Given their frequency along with advancements in screening technologies, various methods are used for the detection of BRAF-mutant cancers. Among these are targeted next-generation sequencing (NGS) on tumor tissue or circulating tumor DNA (ctDNA) and immunohistochemistry (IHC)-based assays. With advancements in detection technologies, several approaches to the treatment of BRAF-mutant cancers have been taken. In this review, we retrace the milestones that led to the clinical development of targeted therapies currently available for these tumors.
自2002年发现以来，BRAF基因突变已被确认为多种癌症类型中明确的致癌驱动因素。目前，其在所有实体瘤中的发生率接近7%，其中BRAF V600E突变约占这些诊断的90%。在黑色素瘤、甲状腺癌和组织细胞肿瘤中，BRAF热点突变的发生率约为50%，而在肺癌和结直肠癌中，其发生率约占报告病例的3%至10%。尽管在乳腺癌和卵巢癌等其他恶性肿瘤中也存在BRAF突变，但其在诊断中所占比例较小（<1%）。鉴于其发生频率以及筛查技术的进步，目前采用多种方法检测BRAF突变癌症，包括对肿瘤组织或循环肿瘤DNA（ctDNA）进行靶向二代测序（NGS）以及基于免疫组织化学（IHC）的检测方法。随着检测技术的发展，针对BRAF突变癌症的治疗已形成多种策略。本文综述了推动当前针对此类肿瘤靶向疗法临床发展的里程碑事件。
Mutations in the Serine/Threonine Kinase BRAF: Oncogenic Drivers in Solid Tumors
肿瘤(癌症)患者之家