Department of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Am Soc Clin Oncol Educ Book. 2021 Mar;41:79-90. doi: 10.1200/EDBK_321137.
This review aims to provide an overview of nonsurgical treatment strategies for central nervous system metastases in melanoma as well as discuss treatment challenges and future directions. Recent strategies for melanoma brain metastases have involved proving the intracranial activity of approved therapies as well as identifying novel drug targets. BRAF/MEK combination therapy has intracranial activity in those with V600 mutations, though disease control is shorter for intracranial than extracranial metastases. Immunotherapy and combination immunotherapies have emerged as providing durable responses in melanoma, and newer studies combining immunotherapy with targeted therapies are emerging. Continued challenges include penetration through the blood-brain barrier and development of resistance mechanisms. Novel therapeutic targets and methods to improve central nervous system penetrance are being identified through the application of deep DNA- and RNA-sequencing analyses. Radiation therapy approaches, especially stereotactic radiosurgery in combination or in sequence with systemic therapies, are also being investigated. Both targeted therapies and immunotherapies have revolutionized the field of melanoma treatment. Multimodality approaches with multidisciplinary teams will pave the way for the future of central nervous system disease treatment in melanoma.
本文旨在综述黑色素瘤脑转移的非手术治疗策略，并讨论治疗挑战和未来方向。黑色素瘤脑转移的最新策略涉及证明已批准疗法在颅内的活性，以及确定新的药物靶点。BRAF/MEK 联合治疗对 V600 突变患者具有颅内活性，但颅内转移的疾病控制时间短于颅外转移。免疫疗法和联合免疫疗法为黑色素瘤提供了持久的缓解，并且新的研究正在将免疫疗法与靶向疗法相结合。持续存在的挑战包括穿透血脑屏障和耐药机制的发展。通过应用深度 DNA 和 RNA 测序分析，正在确定新的治疗靶点和改善中枢神经系统穿透力的方法。放射治疗方法，尤其是立体定向放射外科与全身治疗联合或序贯应用，也在研究中。靶向治疗和免疫疗法都彻底改变了黑色素瘤的治疗领域。多学科团队的多模式方法将为黑色素瘤中枢神经系统疾病治疗的未来铺平道路。
