Synergistic effects of cytotoxic drugs and antiresorptive agents in vitro and in vivo

Breast cancer patients commonly receive a combination of different therapies; however, our understanding of how such combined treatments work is incomplete. In an attempt to optimize treatment strategies we have focused on determining how anticancer agents can be combined in order to induce maximum levels of tumour cell death. The antiresorptive agent zoledronic acid (zol) (Novartis Pharma, Basel, Switzerland) and the chemotherapeutic agent doxorubicin (dox) (Parmachemie BV, Haarlem, The Netherlands) have been shown to synergistically increase apoptosis in breast cancer cells in vitro. In order to determine whether sequential treatment with dox and zol could have potential clinical relevance and to determine the cellular mechanisms responsible for this synergy, we have further investigated combination treatments in vitro and in vivo.