Targeting the S1P Axis and Development of a Novel Therapy for Obesity-Related Triple-Negative Breast Cancer
Technical Report,01 Sep 2014,31 Aug 2019
Virginia Commonwealth University School of Medicine Richmond United States
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More than 40,000 women in the US die each year of metastatic breast cancer, for which there are currently no permanent cures. The majority of breast tumors express the estrogen receptor ER, and anti-estrogens, such as tamoxifen, are the first line of therapy. Unfortunately, half of these patients will ultimately fail therapy due to de novo or acquired resistance, as well as patients with ER, progesterone receptor PR and HER2 triple negative breast cancer TNBC, which is aggressive with high recurrence, metastatic, and mortality rates. Obesity and associated inflammation is now endemic and has been associated with increased risk for lymph node metastasis, endocrine therapy resistance, larger tumors, death, and for presenting with TNBC. However, the links between obesity and breast cancer are not understood and will be investigated here. This proposal will lead to novel therapies that will overcome the overarching challenges of developing safe and effective drugs for treating obesity promoted cancers and TNBC and will identify the bioactive sphingolipid metabolite, sphingosine-1-phosphate S1P, produced by sphingosine kinases SphK1 and SphK2, as a critical factor that links obesity and chronic inflammation to drive breast cancer growth and metastasis.
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- Anatomy and Physiology