Development of Novel Small Molecules Nsc771784 and Nsc772867 for Breast Cancer Therapy with Brain Metastasis

Breast cancer is the most common cancer in Taiwan, and the average age of onset in Taiwanese women is decreasing every year. Brain metastasis of triple negative breast cancer occurs in up to 40% of cases, and is a significant challenge due to resistance to conventional treatments. This study will determine the suitability of two novel small molecule cytotoxic drugs for treating breast cancer and brain metastases. Preliminary data clearly shows that these two candidates have excellent in vitro cytotoxic activity and selectivity against breast cancer and brain cancer cell lines, especially triple negative breast cancer lines. Both molecules are strongly predicted to pass through the blood brain barrier, which would render them useful in treating brain metastasis. However, the efficacy of these drugs in vivo has not been tested. This study aims to fully characterise in vitro activity, as well as examine these molecules for their in vivo efficacy and safety using a variety of mouse xenograft models of primary and metastatic breast cancer. Furthermore, a liposomal formulation of both molecules will be created, which can improve pharmacokinetic properties of the drugs as well as improve uptake and retention by the tumour sites.