Abstract：
The advent of high-throughput sequencing has allowed to profoundly interrogate the molecular landscape of non-small cell lung cancer (NSCLC) in the last years. These findings constitute the opportunity to better stratify these patients in order to address specific treatments to well-defined oncogene-restricted subgroups. Among them, BRAF-mutated lung cancers represent around 4% of NSCLC, thus identifying a clinically relevant population that should be aptly managed. Pivotal phase II trials have demonstrated the efficacy of combinatorial treatment - dabrafenib plus trametinib, targeting both BRAF and MEK - for patients harboring V600E mutations, making this specific BRAF alteration a mandatory requirement in the genetic portrait of advanced non-squamous lung cancer patients. However, around half of BRAF+ NSCLC patients remain orphan of targeted approaches. Here we review the available evidence, mainly from a clinical perspective, of therapeutic strategies for both V600E and non-V600 patients, in terms of small molecule, immune checkpoint inhibitors and forthcoming integrated strategies. Looking at on-going clinical trials, a special attention is dedicated to emergent molecules and combinatorial strategies that not only will improve outcomes of classical V600E, but also will make concrete the chance of tailored treatments for the majority of BRAF-mutated patients.
摘要：
高通量测序的出现已经允许在过去几年中深刻地询问非小细胞肺癌(NSCLC)的分子景观。这些发现构成了更好地对这些患者进行分层的机会，以便针对明确定义的癌基因限制性亚组进行特定治疗。其中,BRAF突变的肺癌约占NSCLC的4％，从而确定一个临床相关的人群，应该适当管理。关键的II期试验已经证明了联合治疗的疗效-达拉非尼加曲美替尼，靶向BRAF和MEK-对于携带V600E突变的患者，使这种特定的BRAF改变成为晚期非鳞状细胞肺癌患者遗传肖像中的强制性要求。然而,大约一半的BRAF+NSCLC患者仍然是靶向治疗的孤儿.在这里，我们回顾了现有的证据，主要从临床的角度来看，V600E和非V600患者的治疗策略，就小分子而言，免疫检查点抑制剂和即将到来的综合策略。看看正在进行的临床试验，特别关注新兴分子和组合策略，这不仅会改善经典V600E的结果，而且还将为大多数BRAF突变患者提供量身定制的治疗方法。
