Peloruside A is a microtubule-
stabilizing agent isolated from a New Zealand marine sponge. Peloruside prevents growth of a panel of
cancer cell lines at low nanomolar concentrations, including cell lines that are resistant to
paclitaxel. Three xenograft studies in athymic nu/nu mice were performed to assess the efficacy of peloruside compared with standard
anticancer agents such as
paclitaxel,
docetaxel, and
doxorubicin. The first study examined the effect of 5 and 10 mg/kg peloruside (QD×5) on the growth of H460
non-small cell lung cancer xenografts. Peloruside caused
tumor growth inhibition (%TGI) of 84% and 95%, respectively, whereas standard treatments with
paclitaxel (8 mg/kg, QD×5) and
docetaxel (6.3 mg/kg, Q2D×3) were much less effective (%TGI of 50% and 18%, respectively). In a second xenograft study using A549
lung cancer cells and varied schedules of dosing, activity of peloruside was again superior compared with the
taxanes with inhibitions ranging from 51% to 74%, compared with 44% and 50% for the two
taxanes. A third xenograft study in a
P-glycoprotein-overexpressing NCI/ADR-RES
breast tumor model showed that peloruside was better tolerated than either
doxorubicin or
paclitaxel. We conclude that peloruside is highly effective in preventing the growth of lung and
P-glycoprotein-overexpressing
breast tumors in vivo and that further therapeutic development is warranted. Mol
Cancer Ther; 14(8); 1816-23. ©2015 AACR.