Editors' ChoiceCancer

Blocking transcription in tumors, STAT

Sci. Signal.  24 Nov 2015:
Vol. 8, Issue 404, pp. ec351
DOI: 10.1126/scisignal.aad9035

STAT3 is a transcription factor that plays an oncogenic role in many cancers, but STAT3 has proven difficult to target with chemical inhibitors. Hong et al. demonstrated that antisense technology is a feasible alternative to small-molecule inhibitors for targeting STAT3. The authors used high-affinity, next-generation antisense oligonucleotides, which have higher potency than previous generations and can be systemically administered without a lipid vehicle. One of these new antisense oligonucleotides, AZD9150, demonstrated activity in various preclinical cancer models, as well as in cancer patients who had failed one or more previous treatments, paving the way for additional clinical testing of this therapy.

D. Hong, R. Kurzrock, Y. Kim, R. Woessner, A. Younes, J. Nemunaitis, N. Fowler, T. Zhou, J. Schmidt, M. Jo, S. J. Lee, M. Yamashita, S. G. Hughes, L. Fayad, S. Piha-Paul, M. V. P. Nadella, M. Mohseni, D. Lawson, C. Reimer, D. C. Blakey, X. Xiao, J. Hsu, A. Revenko, B. P. Monia, A. R. MacLeod, AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer. Sci. Transl. Med. 7, 314ra185 (2015). [Abstract]