Sharma Akanksha, Singer Lauren, Kumthekar Priya
Department of Translational Neurosciences, Pacific Neuroscience Institute, Saint John Cancer Institute, Santa Monica, CA 90404, USA.
Malnati Brain Tumor Institute at the Robert H. Lurie Comprehensive Cancer Center, Department of Neurology at the Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Cancers (Basel). 2021 Dec 21;14(1):17. doi: 10.3390/cancers14010017.
Central nervous system (CNS) metastases can occur in a high percentage of systemic cancer patients and is a major cause of morbidity and mortality in these patients. Almost any histology can find its way to the brain, but lung, breast, and melanoma are the most common pathologies seen in the CNS from metastatic disease. Identification of many key targets in the tumorigenesis pathway has been crucial to the development of a number of drugs that have demonstrated successful penetration of the blood-brain, blood-cerebrospinal fluid, and blood-tumor barriers. Targeted therapy and immunotherapy have dramatically revolutionized the field with treatment options that can provide successful and durable control of even CNS disease. In this review, we discuss major targets with successful treatment options as demonstrated in clinical trials. These include tyrosine kinase inhibitors, monoclonal antibodies, and antibody-drug conjugates. We also provide an update on the state of the field and highlight key upcoming trials. Patient-specific molecular information combined with novel therapeutic approaches and new agents has demonstrated and continues to promise significant progress in the management of patients with CNS metastases.
中枢神经系统（CNS）转移可发生于高比例的全身性癌症患者中，并且是这些患者发病和死亡的主要原因。几乎任何组织学类型的癌症都可能转移至脑部，但肺癌、乳腺癌和黑色素瘤是中枢神经系统转移性疾病中最常见的病理类型。肿瘤发生途径中许多关键靶点的鉴定对于多种药物的研发至关重要，这些药物已证明能够成功穿透血脑屏障、血脑脊液屏障和血肿瘤屏障。靶向治疗和免疫治疗通过能够成功且持久地控制甚至中枢神经系统疾病的治疗方案，给该领域带来了巨大变革。在本综述中，我们讨论了临床试验中已证明有效的主要靶点及治疗方案。这些包括酪氨酸激酶抑制剂、单克隆抗体和抗体药物偶联物。我们还提供了该领域的最新进展，并重点介绍了即将开展的关键试验。患者特异性分子信息与新型治疗方法和新药物相结合，已在中枢神经系统转移患者的管理中取得了显著进展，并将继续带来重大突破。
