Death receptor 5 agonist TRA8 in combination with the bisphosphonate zoledronic acid attenuated the growth of breast cancer metastasis

Bone metastasis affects the majority of patients with advanced breast cancer and no adequate therapy exists.  Bisphosphonates, like zoledronic acid, inhibit the osteolytic component of tumor growth in osseous tissues, but these drugs are not curative. The current study evaluated the combination of zoledronic acid with death receptor 5 agonists in an animal model of breast cancer bone metastasis.  Materials and Methods. Female athymic nude mice (age 4-6 weeks, n=35) were inoculated with 200,000 luciferase-positive MDA- MB-435 cells by injection into the left ventricle. Animals were immediately imaged by bioluminescence technique and placed into one of the following therapy groups: Saline, hTRA8, hTRA8 + zoledronic acid, mTRA8, mTRA8 + zoledronic Acid, or zoledronic acid monotherapy. DR5 agonists were given at 200 µg/dose and zoledronic acid 5 µg /dose, with mice treated biweekly for 4.5 weeks and imaged weekly. Results. Combination therapy containing either hTRA8 or mTRA8 with zoledronic acid significantly...