A. GOALS AND OBJECTIVES Please note: only a limited number of literature references are provided throughout the proposal due to space limitations. Introduction. The overall goal of this research is to investigate a novel folate-targeted combination treatment as a translational approach for the ablation of triple-negative breast cancer (TNBC) disease. Over 200,000 new cases of breast cancer are diagnosed annually in the US; approximately 40,000 women die due to the disease. Two women die every day of breast cancer in the state of Arizona, while over 4600 cases are diagnosed every year (American Cancer Society). Surgical resection is typically the primary treatment, and chemotherapy is the treatment of choice for steroid receptor-negative tumors. Primary chemotherapy is used in cases of locally advanced and operable breast cancer. However, the disease recurs in over 50% treated cases, and approximately 20-60% of the affected women eventually develop advanced metastatic disease, which leads to mortality. Triple-negative breast cancer (TNBC) occurs in approximately 15-30% breast cancer patients, and is characterized by lack of expression of the progesterone, estrogen and HER2 receptors. TNBC, arguably the most difficult form of breast cancer to treat, is associated with poor prognosis, limited therapeutic options, and no targeted therapies. TNBC patients do not respond to endocrine therapy or trastuzumab. The failure of iniparib, a PARP inhibitor, in Phase III clinical trials, further limits therapeutic options. Recent (2012) findings indicate that 70-80% stage IV metastatic TNBC cells show strong expression of the folate receptor (FR)- alpha, which allows for novel targeted therapeutics against TNBC. TNF-alpha Related Apoptosis Inducing Ligand (TRAIL) is a death ligand (DL) that selectively induces apoptosis in malignant cells over normal cells upon binding death receptors (DRs). Despite this selectivity, cancer cells are resistant to TRAIL-induced death, and therefore, co
|Effective start/end date||10/1/15 → 10/22/19|
- Arizona Biomedical Research Commission: $658,244.00
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