Manipulating Redox Signaling to Block Tumor Angiogenesis

A tumor consists of a population of rapidly dividing and growing cancer cells. Cancer cells have lost their ability to divide in a controlled fashion and as a consequence they rapidly accumulate mutations. In such way cancer cells (or sub-populations of cancer cells within a tumor) will acquire stronger proliferative capacity [1]. Tumors cannot grow beyond a certain size due to a lack of oxygen and other essential nutrients. Tumors cells have then acquired a specific feature that is to induce blood vessel growth, a process called tumor angiogenesis. Tumor angiogenesis is a necessary and required step for transition from a small harmless cluster of cells to a large tumor [2]. The early induction of tumor vasculature is termed “angiogenic switch”, that occurs when a tumor mass reaches about dimensions of 2 mm2 and moves towards progression. The “angiogenic switch” is a rate-limiting step for tumor growth that is not limited at earliest stages, but occurs also at different stages of tumor-progression. The angiogenic switch induces angiogenic sprouting and new vessels formation and matura‐ tion. Activation of angiogenesis in premalignant lesions and dormant metastasis is mandatory for tumor survival. The fact that tumor mass is depending on angiogenesis has driven the medical research towards the characterization of molecular pathways and cellular dynamics for the induction and regulation of angiogenesis.