Novel Antiangiogenic/Cytotoxic Therapies for Advanced Breast Cancer

摘要

Incontrovertible evidence now exists that the growth of 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 mediator, named angiogenin (Ang), in human breast cancer cells and are developing inhibitors of its functions. In order to evaluate whether these inhibitors may be useful for treating breast cancer, we have during the grant period developed mouse models for both primary and metastatic growth of human breast cancer cells. Using these models we have shown that Ang antagonists (including monoclonal antibodies and antisense reagents) potently interfere with the establishment and metastatic spread of breast cancer cells. Further generation drugs, which include small molecule inhibitors, humanized antibodies and peptide mimetic drugs, are under development for eventual testing. In addition, multimodal therapies combining antiAng agents with conventional chemotherapeutic drugs will be evaluated in the future. Importantly, interest in this therapeutic approach has generated an intent to form a biotechnology company dedicated to translating these preclinical findings into treatment and prevention trials in patients.