Targeting and inhibition of tumor-associated macrophages in breast cancer

Breast cancer is a disease which affects 1 in 7 women during their lifetime. With 464.000 new cases and 131.000 deaths, it is the most occurring cancer type and leading cause of cancer related deaths in women in Europe. As the overall age of the population is predicted to increase, these numbers will rise as well. Cytotoxic agents, hormone treatment, radiation and small molecule inhibitors are the current therapies used in the treatment of breast cancer. Although these therapies work well towards the primary tumor, they do not affect the surrounding stromal cells. Tumor growth and survival depend greatly on the support of the tumor micro-environment (TME), where stromal cells promote neo-angiogenesis, matrix remodeling and cause suppression of the adaptive immune system. Macrophages play a major role in these processes. Tumor-associated macrophages (TAM), present in the TME, have been shown to play a crucial role in tumor growth and progression. Therefore, effective treatment of TAM might prove to be a successful treatment strategy in breast cancer therapy. This thesis project aimed to develop a novel nanoparticle-based strategy to target TAM and inhibit their tumor growth promoting activities. A novel drug candidate (AS1517499) was identified for such inhibition, and incorporated into a newly designed nanoparticle delivery system, which was able to selectively deliver TAM-modulating drugs to TAM