Current Challenges of Cancer Anti-angiogenic Therapy and the Promise of Nanotherapeutics.

With growing interest in cancer therapeutics, anti-angiogenic therapy has received considerable attention and is widely administered in several types of human cancers. Nonetheless, this type of therapy may induce multiple signaling pathways compared with cytotoxics and lead to worse outcomes in terms of resistance, invasion, metastasis, and overall survival (OS). Moreover, there are important challenges that limit the translation of promising biomarkers into clinical practice to monitor the efficiency of anti-angiogenic therapy. These pitfalls emphasize the urgent need for discovering alternative angiogenic inhibitors that target multiple angiogenic factors or developing a new drug delivery system for the current inhibitors. The great advantages of nanoparticles are their ability to offer effective routes that target the biological system and regulate different vital processes based on their unique features. Limited studies so far have addressed the effectiveness of nanoparticles in the normalization of the delicate balance between stimulating (pro-angiogenic) and inhibiting (anti-angiogenic) factors. In this review, we shed light on tumor vessels and their microenvironment and consider the current directions of anti-angiogenic and nanotherapeutic treatments. To the best of our knowledge, we consider an important effort in the understanding of anti-angiogenic agents (often a small volume of metals, nonmetallic molecules, or polymers) that can control the growth of new vessels.