Development of therapies to treat breast cancer is an important challenge because breast cancer is a leading cause of cancer-related deaths in women in the United States. Every year, there are about 40,000 breast cancer deaths in the United States. Accordingly, breast cancer is one of the most important health issues facing women in the United States. Considerable information is known about cell signaling in breast cancer and metastasis, Epithelial-Mesenchymal Transition (EMT) is a critical event in progression toward breast cancer metastasis with down-regulation of epithelial markers and up-regulation of mesenchymal markers. EMT is also involved in the onset of breast cancer drug resistance and tumor relapse that is characterized as escape from apoptosis with poor prognosis. Thus, there is an urgent major unmet medical need for the development of specific, inexpensive and convenient targeted treatments for breast cancer. Medicinal chemistry refinement has resulted in a drug-like lead compound that has shown much promise as a compound that inhibits breast cancer cell proliferation in vitro. The work proposed is transformative because the lead compound simultaneously blocks three distinct mechanisms for breast cancer cell invasion, controls one target through multiple mechanisms, selectively inhibits a prominent signaling associated with breast cancer and potentially decreases chemoresistance.
The current program will develop the lead compound and test the feasibility of this lead as a new approach to stopping breast cancer. This approach takes advantage of a highly selective approach that circumvents major limitations of currently available agents. The novelty of this project comes from the unique drugable target of the proposed anti-cancer compounds. The proposed target is directly linked to cancer cell proliferation and we postulate that compounds targeting this component of dysregulated signal transduction could afford very efficacious anti-cancer therapies with minimal adverse effects.
The results obtained will be crucial to development of novel treatments for breast cancer that currently represents a significant medical need. We hypothesize that the lead compound will inhibit breast cancer proliferation in in vivo xenograft animal model studies with minimal side effects, thus providing evidence of novel therapeutic utility.