Manipulating the Tumor Microenvironment: Opportunities for Therapeutic Targeting

Over the years, there has been a marked change in the modalities of cancer treatment from the use of surgery and radiation therapy as gold standards to the employment of chemotherapy and combination approaches using a variety of modalities. Despite the advances, prognosis generally remains poor due to patients who develop toxicity or become refractory to therapy. The focus of treatment approaches has largely been on eliminating tumor cells. However, recent studies have shown that there is cross talk between tumor cells and their immediate environment, collectively known as the tumor microenvironment (TME). The TME contributes to certain characteristics of cancer such as hyperproliferation and angiogenesis. As such, the TME has been recognized as an important contributor to cancer progression, cellular invasion and metastatic dissemination. In addition, the TME has been reported to promote adaptive resistance to therapy in a number of cancers. Herein, we provide a brief overview of the pathophysiology of aspects of the tumor microenvironment. We further review emerging treatment modalities that target this niche and the mechanisms underpinning the efficacy of these therapies.

Keywords: Angiogenesis, Cancer, Chemotherapy, Drug delivery, Endothelial cells, Extracellular matrix, Targeted therapy, Tumor associated fibroblasts, Tumor associated macrophages, Tumor microenvironment.