Tumor microenvironment: A key contributor to cancer progression, invasion, and drug resistance

The tumor microenvironment is composed of extracellular matrix proteins, mostly collagen, and a wide range of tumor-associated cells, including fibroblasts, neutrophils, macrophages, and blood vessels. These components play a crucial role in supporting tumor growth and proliferation, especially at the early stages of metastasis, as well as determine the physiology of tumor cells. Within the tumor microenvironment, the interaction between tumor cells and tumor-associated cells does not only lead to tumor growth and metastasis, but also induces the epithelial-mesenchymal transition and angiogenesis and contributes to the development of drug and radiation treatment resistance. Ion channels and transporters are the important elements in the drug resistance of tumor cells. Advancing our understanding of the tumor microenvironment and its processes encouraging tumor progression is of paramount importance for creating effective targeted antitumor drugs of high specificity, i.e., drugs suppressing stromal and immune components of the tumor microenvironment, as well as at extracellular matrix, angiogenic factors, ion channels and transporters. In this review, we describe the main processes and interactions taking place in the tumor microenvironment and influencing the efficacy of antitumor therapy. We also take a look at stromal and immune cells involved in the tumor development and factors mediating the drug resistance in patients with cancer.