Optimization of tumor immunotherapy in breast carcinoma. Tumor microvasculature normalization: blood vessels' endothelium

Abstract

Breast cancer is one of the most common and malignant cancers nowadays. Like many cancers, it is extensively regulated by pro-angiogenic and pro-lymphangiogenic factors, which induce rapid vasculature growth. This results in aberrant vessels which enhance a pro-tumor environment by preventing treatment against cancer to get to the tumor, inducing the malignancy of cancer cells, and inhibiting the immune response. In the last years, antiangiogenic treatment was suggested as a possible way to eliminate the tumor-supporting environment. This approach was soon replaced by the judicious use of these anti-angiogenic molecules in normalizing concentrations, to prevent pro-tumor effects, such as cell malignification. In a novel approach to prevent these processes to occur, we have designed a treatment based on the normalization of the tumoral vasculature of triple-negative breast carcinoma, so they return to their physiological state. For this aim, we have analyzed the effects of the blockage of VEGF-A and VEGF-C signaling pathways (angiogenesis and lymphangiogenesis), by targeting their receptors, VEGFR2 and VEGFR3, with inhibitor molecules (DC101 antibody and SAR131675 molecules).