Thursday, December 5, 2013
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Toll-like receptor 9
(TLR9); signal transducer and activator of transcription 3
Mouse studies suggest
inhibitors of TLR9 or STAT3 could help prevent tumor recurrence after
radiation therapy. In radiation-treated mice bearing melanoma, bladder or
colorectal tumors, Tlr9 knockout decreased activation of Stat3 in
tumor-infiltrating myeloid cells compared with no knockout, thereby
inhibiting tumor revascularization and tumor regrowth. In wild-type mice
bearing those tumor types, radiation and either a TLR9 antagonist or Stat3
small interfering RNA increased the time to tumor regrowth compared with
radiation or targeted therapy alone. Ongoing work includes confirming the
finding in tissue samples from patients with prostate cancer undergoing
Isis Pharmaceuticals Inc.
and AstraZeneca plc have ISIS-STAT3Rx (AZD9150), an antisense
inhibitor of STAT3, in Phase I/II testing to treat solid and blood cancers.
Otsuka Pharmaceutical Co. Ltd.
has OPB-31121, an inhibitor of
STAT3 phosphorylation, in Phase I trials to treat solid tumors.
Dynavax Technologies Corp.
and GlaxoSmithKline plc have DV1179, an inhibitor of
TLR9 and TLR7, in Phase I testing to
treat systemic lupus erythematosus (SLE) and autoimmune and inflammatory
Published online Dec. 5, 2013
Patent application filed by
City of Hope;
available for licensing
Gao, C. et al. Cancer Res.;
published online Oct. 23, 2013;
Contact: Marcin Kortylewski, Beckman Research Institute at
City of Hope, Duarte, Calif.
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