Liquid biopsies to occult brain metastasis

Abstract

Brain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early detection. Liquid biopsy is widely accepted as a non-invasive method for diagnosing cancer and other diseases. We have reviewed the evidence that shows how the molecular alterations are involved in BrM, majorly from breast cancer (BC), lung cancer (LC), and melanoma, with an inception in how they can be employed for biomarker development. We discussed genetic and epigenetic changes that influence cancer cells to breach the blood-brain barrier (BBB) and help to establish metastatic lesions in the uniquely distinct brain microenvironment. Keeping abreast with the recent breakthroughs in the context of various biomolecules detections and identifications, the circulating tumor cells (CTC), cell-free nucleotides, non-coding RNAs, secretory proteins, and metabolites can be pursued in human body fluids such as blood, serum, cerebrospinal fluid (CSF), and urine to obtain potential candidates for biomarker development. The liquid biopsy-based biomarkers can overlay with current imaging techniques to amplify the signal viable for improving the early detection and treatments of occult BrM.

Comparison of the diagnostic value of liquid biopsy in leptomeningeal metastases: A systematic review and meta-analysis

“…Targeted sequencing method could be used to identify oncogene and tumor suppressor mutations. However, they focused on a limited number of genes, and may not represent the full spectrum of clinically relevant oncogenic drivers ( 42 ). With the advance in technological platforms development, expanding the number of genes and improving the sensitivity to detect mutations could improve the sensitivity of liquid biopsies in patients with BM ( 5 ).…”

The Landscape of Biomimetic Nanovesicles in Brain Diseases

“…Although biological components and metabolites are abundant in the circulation, they are susceptible to rapidly metabolize and deplete without protective structures. [ 3 ] BNVs (especially EVs) have shown great promise for liquid biopsy applications recently: a) EVs are specific disease‐derived substances carrying with proteins, DNAs, RNAs, and metabolites, which can reflect disease relative biological behaviors; [ 161 ] b) EVs are highly abundant in blood (≈10 9 particles mL −1 ), improving the detection sensitivity and limitation; [ 162 ] c) the bioinformatics carried by BNVs are protected by phospholipid bilayer, which guarantees their structural and functional integrities. [ 3 ] In addition, the physical properties of BNVs can also be used as an indicator for tumor malignancy.…”

Tumor-derived small extracellular vesicles: potential roles and mechanism in glioma

“…Invasion and metastasis are the important reasons underlying poor tumor prognosis, and their occurrence involves several factors such as weakened adhesion between tumor cells and degradation of extracellular matrix, which can promote tumor metastasis [ 106 , 107 ]. Extracellular matrix (ECM) acts as a natural barrier to tumor invasion and metastasis, and thus effectively prevents tumor metastasis [ 108 , 109 ] (Fig.…”