Biomarkers and focused ultrasound: the future of liquid biopsy for brain tumor patients

Abstract

Introduction Despite advances in modern medicine, brain tumor patients are still monitored purely by clinical evaluation and imaging. Traditionally, invasive strategies such as open or stereotactic biopsies have been used to confirm the etiology of clinical and imaging changes. Liquid biopsies can enable physicians to noninvasively analyze the evolution of a tumor and a patient’s response to specific treatments. However, as a consequence of biology and the current limitations in detection methods, no blood or cerebrospinal fluid (CSF) brain tumor-derived biomarkers are used in routine clinical practice. Enhancing the presence of tumor biomarkers in blood and CSF via brain-blood barrier (BBB) disruption with MRI-guided focused ultrasound (MRgFUS) is a very compelling strategy for future management of brain tumor patients. Methods A literature review on MRgFUS-enabled brain tumor liquid biopsy was performed using Medline/Pubmed databases and clinical trial registries. Results The therapeutic applications of MRgFUS to target brain tumors have been under intense investigation. At high-intensity, MRgFUS can ablate brain tumors and target tissues, which needs to be balanced with the increased risk for damage to surrounding normal structures. At lower-intensity and pulsed-frequency, MRgFUS may be able to disrupt the BBB transiently. Thus, while facilitating intratumoral or parenchymal access to standard or novel therapeutics, BBB disruption with MRgFUS has opened the possibility of enhanced detection of brain tumor-derived biomarkers. Conclusions In this review, we describe the concept of MRgFUS-enabled brain tumor liquid biopsy and present the available preclinical evidence, ongoing clinical trials, limitations, and future directions of this application.

Focused Delivery of Chemotherapy to Augment Surgical Management of Brain Tumors

“…However, using MRgFUS to open the BBB could increase the concentration of tumor-derived biomarkers within the CSF. This would noninvasively allow physicians to monitor the development of a tumor [ 138 ]. Moreover, microbubble-enhanced focused ultrasound is a newly developing technology that may disrupt the BBB in a more efficient manner—allowing for the delivery of chemotherapeutic drugs [ 139 ].…”

Predictive Value of Blood Markers in Pediatric Brain Tumors Using Machine Learning

“…Circulating tumor cells, free-cell DNA, microRNA, and extracellular vesicles have been studied in brain tumors [42][43][44]. Despite advances in liquid biopsy, it has not become a daily practical method [45]. Biomarkers that are effective in diagnosis and follow-up of brain tumors are challenged.…”

Low-Intensity Focused Ultrasound Technique in Glioblastoma Multiforme Treatment

“…The BBB/BTB hinders the influx of substances into the CNS while simultaneously hindering the egress of tumor biomarkers into the peripheral circulation ( 105 ). This poses a major limitation in the molecular diagnosis of glioblastomas leaving only stereotactic biopsies as a way for analysis which is both invasive and poses the risk of infiltration to other parts of the brain, without forgetting the risk of infection ( 105 ).…”

“…The BBB/BTB hinders the influx of substances into the CNS while simultaneously hindering the egress of tumor biomarkers into the peripheral circulation ( 105 ). This poses a major limitation in the molecular diagnosis of glioblastomas leaving only stereotactic biopsies as a way for analysis which is both invasive and poses the risk of infiltration to other parts of the brain, without forgetting the risk of infection ( 105 ). Fortunately, in the same way that BBB/BTB disruption allows substances to cross through the BBB/BTB into the brain, there is also the possibility of other substances to spill in the intravascular circulation vice-versa (as shown in Figure 3C with orange full arrow).…”