Combined effects on tumor growth and metastasis by anti-estrogenic and antiangiogenic therapies in MMTV-neu mice

Breast tumor growth and metastatization are both hormone sensitive and angiogenesis dependent. Recent work carried out in our laboratory on a transgenic model of breast cancer displaying many similarities to its human counterpart, has showed that liposome-mediated angiostatin cDNA delivery partially inhibits both local and metastatic growth. However, it is now recognized that anti-angiogenesis strategy alone cannot completely arrest tumor growth and spread, and this led to the suggestion that approaches based on different molecular mechanisms could usefully be combined. In the present work, we investigated whether Tamoxifen, a classical antiestrogen agent widely used in human therapy, could improve the results obtained with angiostatin alone. Further reduction of local growth was achieved with the combined regimen with respect to angiostatin or tamoxifen alone, while, as expected, no metastatic growth was detected in both groups. We therefore conclude that a combination of angiogenesis inhibitors with antiestrogen drugs might be useful in humans; and that other associations between conventional and gene transfer-mediated therapy are worth investigating and will soon become important components of anticancer therapy