Metastases to the central nervous system (CNS) are common in several
cancer types. For most primary
tumors that commonly metastasize to the CNS, molecular
biomarker analyses are recommended in the clinical setting for selection of appropriate targeted
therapies. Therapeutic efficacy of some of these agents has been documented in patients with
brain metastases, and molecular testing of CNS
metastases should be considered in the clinical setting. Here, we summarize the clinically relevant
biomarker tests that should be considered in neurosurgical specimens based on the current recommendations of the European Society of Medical Oncology (ESMO) or the National Comprehensive
Cancer Network (NCCN) for the most relevant primary
tumor types:
lung cancer (EGFR mutations, ALK rearrangement, BRAF mutations),
breast cancer (HER2 amplification,
steroid receptor overexpression),
melanoma (BRAF mutations), and
colorectal cancer (RAS mutations). Furthermore, we discuss emerging therapeutic targets including novel oncogenic alterations (ROS1 rearrangements, FGFR1 amplifications, CMET amplifications, and others) and molecular features of the tumor microenvironment (including
immune-checkpoint molecules such as CTLA4 and PD-1/PD-L1). We also discuss the potential role of advanced
biomarker tests such as next-generation sequencing and "liquid biopsies" for patients with CNS
metastases.