RNA-directed antisense and interference
therapeutics are a promising treatment option for
cancer. The demonstration of depletion of target
proteins within human
tumors in vivo using validated methodology will be a key to the application of this technology. Here, we present a flow cytometric-based approach to quantitatively determine
protein levels in solid
tumor material derived by fiber optic brushing (FOB) of
non-small cell lung cancer (NSCLC) patients. Focusing upon the
survivin protein, and its depletion by an
antisense oligonucleotide (ASO) (
LY2181308), we show that we can robustly identify a subpopulation of
survivin positive
tumor cells in FOB samples, and, moreover, detect
survivin depletion in
tumor samples from a patient treated with
LY2181308.
Survivin depletion appears to be a result of treatment with this ASO, because a
tumor treated with conventional cytotoxic
chemotherapy did not exhibit a decreased percentage of
survivin positive cells. Our approach is likely to be broadly applicable to, and useful for, the quantification of
protein levels in
tumor samples obtained as part of clinical trials and studies, facilitating the proof-of-principle testing of novel targeted
therapies.