Tan Aaron C, Itchins Malinda, Khasraw Mustafa
Division of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore.
Department of Medical Oncology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
Int J Mol Sci. 2020 Feb 19;21(4):1416. doi: 10.3390/ijms21041416.
The management of non-small cell lung cancer (NSCLC) has transformed with the discovery of therapeutically tractable oncogenic drivers. In addition to activating driver mutations, gene fusions or rearrangements form a unique sub-class, with anaplastic lymphoma kinase () and c-ros oncogene 1 () targeted agents approved as the standard of care in the first-line setting for advanced disease. There are a number of emerging fusion drivers, however, including neurotrophin kinase (), rearrangement during transfection (), and neuregulin 1 () for which there are evolving high-impact systemic treatment options. Brain metastases are highly prevalent in NSCLC patients, with molecularly selected populations such as epidermal growth factor receptor () mutant and -rearranged tumors particularly brain tropic. Accordingly, there exists a substantial body of research pertaining to the understanding of brain metastases in such populations. Little is known, however, on the molecular mechanisms of brain metastases in those with other targetable fusion drivers in NSCLC. This review encompasses key areas including the biological underpinnings of brain metastases in fusion-driven lung cancers, the intracranial efficacy of novel systemic therapies, and future directions required to optimize the control and prevention of brain metastases.
随着可治疗的致癌驱动因素的发现，非小细胞肺癌（NSCLC）的管理发生了变革。除了激活驱动突变外，基因融合或重排形成了一个独特的亚类，其中间变性淋巴瘤激酶（ALK）和c-ros原癌基因1（ROS1）靶向药物被批准作为晚期疾病一线治疗的标准。然而，还有许多新出现的融合驱动因素，包括神经营养激酶（NTRK）、转染期间重排（RET）和神经调节蛋白1（NRG1），针对这些因素有不断发展的高影响力全身治疗选择。脑转移在NSCLC患者中非常普遍，分子选择的人群，如表皮生长因子受体（EGFR）突变和ALK重排的肿瘤尤其具有脑趋向性。因此，存在大量关于此类人群脑转移理解的研究。然而，对于NSCLC中具有其他可靶向融合驱动因素的患者脑转移的分子机制知之甚少。本综述涵盖了关键领域，包括融合驱动肺癌脑转移的生物学基础、新型全身疗法的颅内疗效，以及优化脑转移控制和预防所需的未来方向。
