Abstract
One of the greatest challenges in neuro-oncology is diagnosis and therapy (theranostics) of leptomeningeal metastasis (LM), brain metastasis (BM) and brain tumors (BT), which are associated with poor prognosis in patients. Retrospective analyses suggest that cerebrospinal fluid (CSF) is one of the promising diagnostic targets because CSF passes through central nervous system, harvests tumor-related markers from brain tissue and, then, delivers them into peripheral parts of the human body where CSF can be sampled using minimally invasive and routine clinical procedure. However, limited sensitivity of the established clinical diagnostic cytology in vitro and MRI in vivo together with minimal therapeutic options do not provide patient care at early, potentially treatable, stages of LM, BM and BT. Novel technologies are in demand. This review outlines the advantages, limitations and clinical utility of emerging liquid biopsy in vitro and photoacoustic flow cytometry (PAFC) in vivo for assessment of CSF markers including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNA (miRNA), proteins, exosomes and emboli. The integration of in vitro and in vivo methods, PAFC-guided theranostics of single CTCs and targeted drug delivery are discussed as future perspectives.
Highlights
Leptomeningeal and brain metastasis (LM and BM) as a result of metastatic dissemination of solid tumors and hematological neoplasms as well as primary brain tumors (BTs, e.g., glioma) are commonly fatal with minimum treatmentCells 2019, 8, 1195; doi:10.3390/cells8101195 www.mdpi.com/journal/cellsCells 2019, 8, 1195 options [1,2,3,4,5,6,7,8,9,10,11]
blood-brain barrier (BBB) to penetrate tumor cells [41]), circulating tumor cells (CTCs), their aggregates and other tumor-derived markers may invade cerebrospinal fluid (CSF) through different mechanisms that include (1) crossing the compromised BBB by blood and lymphatic CTCs and/or (2) shedding tumor cells by existing BM and BT. The latter mechanism provides a solid basis for using CSF tumor markers to diagnose progression of BM and BT, and to estimate responses to therapy
Tumor markers in CSF are urgently needed to prolong life of patients suffering from central nervous system (CNS) tumor lesions
Summary
Leptomeningeal and brain metastasis (LM and BM) as a result of metastatic dissemination of solid tumors (e.g., melanoma, breast cancer, lung cancer and colorectal cancer) and hematological neoplasms as well as primary brain tumors (BTs, e.g., glioma) are commonly fatal with minimum treatment. BBB to penetrate tumor cells [41]), CTCs, their aggregates and other tumor-derived markers may invade CSF through different mechanisms that include (1) crossing the compromised BBB by blood and lymphatic CTCs and/or (2) shedding tumor cells by existing BM and BT. The latter mechanism provides a solid basis for using CSF tumor markers to diagnose progression of BM and BT, and to estimate responses to therapy. Testing CSF might predict deadly LM, BM and BT; and advanced methods to assess CSF tumor markers in CSF are urgently needed to prolong life of patients suffering from CNS tumor lesions
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