A brain metastasis liquid biopsy – Where are we now?

Brain metastases remain a challenging and feared complication for patients with cancer and research in this area has lagged behind research into metastases to other organs. Due to their location and the risks associated with neurosurgical biopsies, the biology underpinning brain metastases response to treatment and evolution over time remains poorly understood. Liquid biopsies are proposed to overcome many of the limitations present with tissue biopsies, providing a better representation of tumour heterogeneity, facilitating repeated sampling, and providing a non-invasive assessment of tumour biology. Several different liquid biopsy approaches have been investigated including circulating tumour cells, circulating tumour DNA, extracellular vesicles, and tumour educated platelets; however, these have generally been less effective in assessing brain metastases compared to metastases to other organs requiring improved techniques to investigate these approaches, studies combining different liquid biopsy approaches and/or novel liquid biopsy approaches. Through this review we highlight the current state of the art and define key unanswered questions related to brain metastases liquid biopsies.