A DNA Aptamer That Inhibits the Aberrant Signaling of Fibroblast Growth Factor Receptor in Cancer Cells

Growth factor receptors are activated through dimerization by the
binding of their ligands and play pivotal roles in normal cell function.
However, the aberrant activity of the receptors has been associated
with cancer malignancy. One of the main causes of the aberrant receptor
activation is the overexpression of receptors and the resultant formation
of unliganded receptor dimers, which can be activated in the absence
of external ligand molecules. Thus, the unliganded receptor dimer
is a promising target to inhibit aberrant signaling in cancer. Here,
we report an aptamer that specifically binds to fibroblast growth
factor receptor 2b and inhibits the aberrant receptor activation and
signaling. Our investigation suggests that this aptamer inhibits the
formation of the receptor dimer occurring in the absence of external
ligand molecules. This work presents a new inhibitory function of
aptamers and the possibility of oligonucleotide-based therapeutics
for cancer.