Novel Antiangiogenic/Cytotoxic Therapies for Advanced Breast Cancer (95 Breast)

摘要

Incontrovertible evidence now exists that the growth of both primary and metastatic breast cancer depends on new blood vessel growth, or angiogenesis. Therefore, inhibition of blood vessel ingrowth into breast tumors should be therapeutically useful. We have detected an angiogenic factor, termed angiogenin (Ang), in human breast cancer cells and are developing inhibitors of its functions. To evaluate efficacy of these inhibitors, preclinical orthotopic models of human breast cancer in female athymic mice are in place in the laboratory. In Year 3 of Department of Defense funding we have demonstrated statistically that Ang antagonists, which include the antisense agent JF2S as well as a neutralizing monoclonal antibody (mAb) 26-2F, are capable of inhibiting the establishment of breast cancer cells injected subcutaneously into the mammary fat pad (mfp) . Further, both of these classes of inhibitors can interfere with and, in certain cases, completely prevent the formation of macro- and microscopic lung metastasis in a model in which primary human breast cancer tumors are vigorously growing in the mfp. These therapeutic agents along with small molecule drugs and humanized antibodies under development should therefore be useful clinically for breast cancer therapy and prevention.