The article, "The Novel Triterpenoid C-28 Methyl Ester of 2-Cyano-3, 12-Dioxooleen-1, 9-Dien-28-Oic Acid Inhibits Metastatic Murine Breast Tumor Growth through Inactivation of STAT3 Signaling," was authored by Reata scientific collaborators from the University of Texas M. D. Anderson Cancer Center.
The authors conducted two studies of RTA 402 in the highly rigorous 4T1 mouse model of breast cancer. Few other agents have shown any effect in this animal model, in which tumors grow very rapidly and become widely distributed, or metastasized, throughout the body. In two separate experiments, treatment with RTA 402 was found to have a profound effect in suppressing the growth and spread of these tumors. In a model mimicking the spread of metastatic disease, RTA 402 completely blocked the development of metastases in all animals, whereas untreated animals developed widespread disease. In a second model mimicking the treatment of established breast tumors, RTA 402 provided a 95% reduction in the total tumor burden of treated animals compared with the untreated control group.
Additionally, the authors showed that this activity was occurring in part through inactivation of STAT3 signaling. STAT3 - short for signal transducer and activator of transcription 3 - is increasingly recognized as an important target for cancer therapies. Activated STAT3 is frequently found in patients with breast cancer and other types of tumors. This protein is known to turn on a number of genes associated with cancer growth, invasion, and metastasis. It has also been shown to have a role in preventing the patient's immune system from recognizing and destroying the tumor. It is thought that cancer therapies able to inhibit STAT3 may have profound anti-cancer effects, which may include re-establishing normal immune function against the tumor. The 4T1 animal studies, which are performed in mice that have a normal immune system, provide support for this idea. When researchers examined the spleens of tumor-bearing animals, they found that untreated control animals had a significant reduction in the number of immune cells in their spleens. Animals receiving RTA 402, however, had levels of immune cells that were consistent with healthy, cancer-free animals.
"This paper provides important new data on how RTA 402 works to inhibit the growth and metastasis of cancer," said Warren Huff, CEO of Reata. "The effects on STAT3 shown in this paper, combined with the drugs' proven inhibition of NF-kB, indicate that these agents modulate important and inter-related pathways in cancer cells."
Reata Pharmaceuticals, Inc. is a biopharmaceutical company focused on selecting and discovering promising early drug development opportunities and translating them into successful marketed drugs that target major unmet clinical needs in cancer, inflammation and neurodegenerative disease. The company's two lead programs are entering advanced clinical trials for deadly, late-stage cancers. In parallel with its clinical development, Reata is advancing a breakthrough drug discovery platform that addresses protein misfolding, a key factor in cancer and neurodegenerative disease, to feed its pipeline of small molecule therapeutic candidates. Reata takes a new and different approach to biotechnology, managing its pipeline as a portfolio of opportunities that can be advanced on a single management and physical infrastructure, streamlining the route to human trials and approval. Founded in 2002, Reata is based in the Dallas area. For more information, visit www.reatapharma.com.
For Reata Pharmaceuticals, Inc.
Kathryn Morris, 845-635-9828