Reduced response to radiotherapy significantly hampers tumour control and cure for breast cancer patients. Aside from well-known genetic and epigenetic alterations, increasing evidence points to extracellular matrix interactions as contributors to acquired or developed cancer cell radio-resistance, called cell adhesion-mediated radio-resistance. Our research group observed a dose-dependent increase of collagen type I matrix reorganisation induced by breast cancer cells and associated decrease in radiation-induced breast cancer cells death. Our results for molecular characterisation confirmed the role of focal adhesion components ß1 integrin and focal adhesion kinase in extracellular matrix remodelling and associated radio-resistance. Furthermore, we introduced a new potential target to counteract cell adhesion-mediated radio-resistance, namely non-muscle myosin IIA. The irradiated breast cancer cells were characterised by an increased non-muscle myosin IIA expression and non-muscle myosin IIA-dependent collagen type I reorganisation. Hereby, we hypothesize that extracellular matrix remodelling by irradiated breast cancer cells worsens treatment outcome and can be counteracted by inhibition of non-muscle myosin IIA.