**4. Extracellular matrix in the tumor microenvironment and its impact on cancer therapy**

Solid tumors are complex organ-like structures, that consist not only of tumor cells but also of the vasculature, extracellular matrix (ECM), stromal, and immune cells. Often, this tumor microenvironment (TME) comprises the larger part of the overall tumor mass. Like the other components of the TME, the ECM in solid tumors differ significantly from that of normal organs. Intra-tumoral signaling, transport mechanisms, metabolisms, oxygenation, and immunogenicity are strongly affected if not controlled by the ECM. Exerting this regulatory control, the ECM does not only influence the malignancy and growth of the tumor but also its response toward therapy. Understanding of particularities of the ECM in the solid tumor is required to develop approaches to interfere with its negative effect.

In this chapter, we will also highlight the current understanding of the physical, cellular, and molecular mechanisms by which the pathological tumor ECM affects the efficiency of radiotherapy [1].

The effect of ionizing radiation on cells is also strongly dependent on their oxygenation status. Hypoxia significantly impairs the effectiveness of radiotherapy.
