Growth Factor Receptor-Directed Therapy in Human Breast Cancer

摘要

Overexpression of HER-2 growth factor receptor in human breast cancer is associated with poor prognosis and disease progression. We have targeted these receptor pathways for therapeutic intervention, using a humanized monoclonal antibody to HER-2 receptor (Herceptin). To assess how best to use Herceptin alone and combined with DNA-damaging agents, studies were designed to evaluate its inhibitory effect on cancer growth. The nature of interactions between Herceptin and cytotoxic drugs was evaluated by multiple drug analysis, with in vitro results showing that Herceptin has synergy with cisplatin and thiotepa and additive cytotoxicity with doxorubicin and paclitaxel. Using human breast cancer xenografts in vivo, combination of Herceptin with chemotherapeutic drugs, including cyclophosphamide, paclitaxel or doxorubicin, or with radiation therapy resulted in suppression of breast cancer progression as compared to controls. The additive or synergistic interaction of Herceptin with alkylating agents, cisplatin, taxanes, anthracyclines and radiation therapy in HER-2- overexpressing breast cancer cells suggests that these may be rational combinations for human therapy.