Blood liquid biopsy has emerged as a way of overcoming the clinical limitations of repeat
biopsy by testing for the presence of acquired resistance
mutations to
therapeutic agents. Despite its merits of repeatability and non-invasiveness, this
method is currently only used as a supplemental test due to a relatively low
sensitivity rate of 50%–60%, and cannot replace
tissue biopsy. The circulating
tumor DNAs used in
blood liquid biopsies are passive products of fragmented
DNA with a short
half-life released following
tumor cell death; the low
sensitivity seen with liquid
blood biopsy results from this instability, which makes increasing the
sensitivity of this test fundamentally difficult.
Extracellular vesicles (EVs) are ideal carriers of
cancer biomarkers, as
cancer cells secret an abundance of EVs, and the contents of
tumor cell-originated EVs reflect the molecular and genetic composition of parental
cells. In addition, EV-derived DNAs (EV DNAs) consist of large-sized genomic DNAs and
tumor-specific oncogenic mutant DNAs. For these reasons,
liquid biopsy using EV
DNA has the potential to overcome issues arising from
tissue shortages associated with small
biopsies, which are often seen in
lung cancer patients, and the
biopsy product can be used in other diagnostic
methods, such as
epidermal growth factor receptor (EGFR)
mutation testing and
next-generation sequencing (NGS). A higher
sensitivity can be achieved when EV DNAs obtained from
bronchoalveolar lavage fluid (BALF) are used rather than those from
blood. BALF, when obtained close to the
tumor site, is a promising
liquid biopsy tool, as it enables the gathering of both cellular and non-cellular fractions of the
tumor microenvironment, and provides increased diagnostic
sensitivity when compared to
blood.