Known and emerging biomarkers of leptomeningeal metastasis and its response to treatment.

Leptomeningeal metastasis (LM) is the metastatic dissemination of malignant cells to the leptomeninges and the subarachnoid space of the CNS, affecting approximately 8% of all cancer patients. Cerebrospinal fluid cytology is currently the gold standard for diagnosis of LM and assessment of treatment response, but it has relatively low sensitivity. Thus, specific biomarkers of LM may allow for earlier diagnosis and treatment. This article reviews known tumor markers for LM and describes recent work to find LM-specific markers, such as angiogenesis-related proteins. Novel methods of protein profiling that may aid this search are also described; these methods still need to be standardized and validated to gain widespread acceptance. Nevertheless, we anticipate that future biomarkers will have not only the potential to detect LM, but to predict its progression and response to treatment.