An orally available tubulin inhibitor, VERU-111, to overcome paclitaxel resistance and to suppress breast cancer tumor growth and metastasis.

e13110Background: Triple negative breast cancer (TNBC) is highly aggressive that has poor prognosis due to the development of drug resistance. In this study, we evaluated the preclinical efficacy of the potent tubulin inhibitor, VERU-111, in treating TNBC in mouse xenograft models. Methods: We first conducted in vitro studies to evaluate the anticancer potency and induction of apoptosis of VERU-111 in TNBC cells (MDA-MB-468 and MDA-MB-231). We then determined the efficacy of VERU-111 in MDA-MB-231 cell xenografts into NSG mice. Primary tumor size and body weight of the mice were monitored during the treatment. After 33 days treatment, when the tumor size in the vehicle group reached 1000 mm3, tumors and major organs were collected for histological analysis. Efficacy was also tested in a tail vein injection mouse model and all major organs were collected at 23 days. The degree of tumor necrosis and metastatic burden were determined by H&E staining and cell proliferation, apoptosis and angiogenesis were mea...