Systemic Administration of a Cyclic Signal Transducer and Activator of Transcription 3 (STAT3) Decoy Oligonucleotide Inhibits Tumor Growth without Inducing Toxicological Effects

NF‐κB and stat3 transcription factor signatures differentiate HPV‐positive and HPV‐negative head and neck squamous cell carcinoma

“…50 Oligonucleotide-based therapy, including RNA interference agents and singlestranded decoys have demonstrated specific downregulation of targeted pathways and are actively used in preclinical and early clinical studies to facilitate AP1, RB1, ERs, NF-jB and STATs downregulation. 13,14,51 The correlation of our findings with previous published data suggests that the inferential technique we have developed to define TF activity is robust and a useful tool for discovery of genome-wide changes in TF activity. While we evaluated only the most prominent TF pathways, such as STATs, NF-jB and AP1, many more TFs were found to be significantly and differentially activated in two HNSCC groups.…”

“…However, small peptides and peptidomimetics have shown lower cellular toxicity and better specificity to decrease transcription activity of STAT3, NF‐κB, MYC and others . Oligonucleotide‐based therapy, including RNA interference agents and single‐stranded decoys have demonstrated specific downregulation of targeted pathways and are actively used in preclinical and early clinical studies to facilitate AP1, RB1, ERs, NF‐κB and STATs downregulation …”

“…Therapeutic targeting of TF is complicated due to the low level and cycle‐dependent expression of TF, diversity of posttranscriptional modifications and redundancy of the downstream gene regulation. Despite that, many laboratories have demonstrated efficiency of several anti‐TF therapies, including agents such as bortezomib [targeting NF‐κB through proteasome inhibition], BEZ‐235 [a dual PI3K/mTOR inhibitor], and decoy oligonucleotides [STAT3 and NF‐κB inhibitors] …”

“…Despite that, many laboratories have demonstrated efficiency of several anti-TF therapies, including agents such as bortezomib [targeting NF-jB through proteasome inhibition], 12 BEZ-235 [a dual PI3K/mTOR inhibitor], 6 and decoy oligonucleotides [STAT3 and NF-jB inhibitors]. 13,14 Using high throughput array datasets and the TRANSFAC database, we have developed an inferential method describing TF activity by the gene expression of their targets. 15 Using this method we demonstrate that HPV1 and HPV2 HNSCC are differentiated by the activity of key TFs including STATs and NF-jB.…”

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

“…A number of inhibitors have been developed that appear to directly target the DNA-binding domain of STAT3. Nucleic acid-based drugs, including decoy oligonucleotides and, perhaps, G-quartet oligonucleotides, have been identified that inhibit STAT3-mediated gene expression and inhibit growth of different cancer cell lines (Leong et al, 2003;Lewis et al, 2008;Sun et al, 2008;Shen et al, 2009;Zhang et al, 2013b;Liu et al, 2014;Sen et al, 2014). Platinum IV compounds-CPA-1, CPA-7, IS3 295, and platinum (IV) tetrachloride -also can inhibit STAT3 DNA-binding activity and inhibit cancer cell line growth (Turkson et al, 2004).…”