Updates on Molecular Targeted Therapies for Intraparenchymal CNS Metastases

Simple Summary Metastatic disease to the central nervous system is an advanced-stage complication with historically devastating consequences and high mortality. Significant progress has been made in treatment in the last two decades, especially with the identification and targeting of specific mutations in the cancer pathway. In this review, we provide an updated overview of specific targets and highlight the numerous drugs that have demonstrated penetration and efficacy within the central nervous system. 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.