Chemotaxis Driven Treatment to Reduce Metastasis Post Surgical Resection of Breast Cancer

摘要

It is estimated that there will be 229,060 new cases of invasive breast cancer in the U.S. this year. One of the most aggressive phenotypes, triple negative breast cancer (TNBC) accounts for almost 20% of all breast cancer lesions. Currently, the most effective treatments involve the use of chemotherapeutic drugs such as anthracylines (e.g., doxorubicin) or taxanes (e.g., Taxol); however, despite the sensitivity of TNBCs to these drugs, the overall prognosis is still quite grim as a result of rapid development of resistance and disease recurrence (both locally and distally). For the women diagnosed with TNBC, the most critical aspect of treatment arises from the need to eliminate recurrence and metastasis, which are 15% more likely to occur in TNBC than other forms of breast cancer. Local delivery of chemotherapeutic anthracycline drugs, such as doxorubicin, provides a method by which the concentration of drug at the tumor can be elevated, while simultaneously maintaining low plasma levels of the agent thereby reducing toxicity limitations for the therapy. Additionally, the development of in situ forming implant systems (which are liquid solutions outside of the body, but solidify on contact with an aqueous environment) provides a means by which the implants can be administered under image guidance through a simple injection. While these systems provide an exciting alternative to systemically delivered therapies, they currently cannot address the underlying issue of metastasis. The overall goal of the proposed research is to develop a novel release system designed specifically to treat metastatic breast cancers, and to integrate this release technology into clinical trials for women suffering from triple- negative breast cancer (TNBC).