Target-based Anti-angiogenic Therapy in Breast Cancer

Markus      Wehland; Johann      Bauer; Manfred      Infanger; Daniela      Grimm

doi:10.2174/138161212802430468

Abstract

Breast cancer is the most common female cancer. Despite advances in prevention, early diagnosis, and surgical treatment, its prognosis is still poor. Therefore, immunological and pharmacological methods of treatment have been emphasized recently. Prominent targets of drugs or antibodies are proteins, which are predominantly expressed on breast cancer cells and are simultaneously involved in promoting cell growth or apoptosis. However, breast cancer is a heterogeneous disease, because breast cancer cells may show a variety of malignant gene expression patterns. Therefore, it is difficult at the current state of technology, to apply the optimal cocktail of drugs to hit all cancer cells of any given patient.

Under these circumstances, the option of targeting more tractable, normal cells surrounding the tumor instead of the less heterogeneous ones, preventing them from supporting tumor cell growth, became particularly interesting. Endothelial cells are important supporters of cancer cell growth. As a rule, tumors induce them to grow out and to develop a tumor vasculature, which enables the cancer cells to survive and to spread. The introduction of inhibitors of neovascularization was therefore an important milestone on the way toward treating breast cancer more successfully. It has already been demonstrated that the blockade of vascular endothelial growth results in regression of the disease and first clinical studies seemed to hint toward a beneficial effect on prolongation of survival. Nevertheless, more clinical and basic research is necessary to improve this therapy approach.

This review will compile the knowledge about recently developed anti-angiogenic drugs in the treatment of breast cancer and will provide an overview on currently relevant clinical trials

Keywords: Breast cancer, angiogenesis, vascular endothelial growth factor, tyrosine kinase inhibitor, neoangiogenesis inhibition, prognosis, tumor cell growth, Endothelial cells, anti-angiogenic drugs, clinical trials.