Abstract
Liquid biopsy represents a minimally invasive procedure that can provide similar information from body fluids to what is usually obtained from a tissue biopsy sample. Its implementation in the clinical setting might significantly renew the field of medical oncology, facilitating the introduction of the concepts of precision medicine and patient-tailored therapies. These advances may be useful in the diagnosis of brain tumors that currently require surgery for tissue collection, or to perform genetic tumor profiling for disease classification and guidance of therapy. In this review, we will summarize the most recent advances and putative applications of liquid biopsy in glioblastoma, the most common and malignant adult brain tumor. Moreover, we will discuss the remaining challenges and hurdles in terms of technology and biology for its clinical application.
Highlights
Liquid biopsy represents a minimally invasive procedure that can provide similar information from body fluids to what is usually obtained from a tissue biopsy sample
For Circulating tumor DNA (ctDNA) analyses, plasma samples are preferable to serum ones because they represent a good source of ctDNA and lack background levels of cfDNA, which are higher in serum probably due to contamination with DNA released from immune cells lysed during the clotting process [18]
341 cancer-associated genes in the cerebrospinal fluid (CSF) ctDNA from patients with primary brain tumor or metastases from solid tumors, but not from patients without central nervous system (CNS) affection by cancer [111]. These results suggest that CSF better captures genomic alterations and that is more representative of glioblastoma genetic alterations than plasma ctDNA, recapitulating the mutations from tissue samples
Summary
Glioblastoma is the most frequent, malignant and lethal primary brain tumor in adults. Classical and mesenchymal glioblastomas present improved survival rates that correlate with their better response to conventional therapy, whereas this therapy does not improve the survival in patients with the proneural subtype, this group presents the best outcome [7]. Such an outcome is explained by the global pattern of hypermethylation, referred to as the glioma-CpG island methylator phenotype or G-CIMP, which is closely related to the presence of IDH1/2 mutations [8,9]. The dismal prognosis of glioblastoma highlights the need to unravel the critical molecular mechanisms underlying its progression to develop novel personalized therapeutic strategies
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