The ambiguity of brain metastasis response to radiotherapy driven by cellular adhesion molecules

Brain metastases treatments are usually based on surgery and radiation therapies with poor patient survival. Cellular adhesion molecules (CAMs) are promiscuous proteins highly involved in tumour progression. Owing to their dual functionality in structure and signalling, CAMs have emerged as potential targets in the clinic. It has been shown that CAMs can modulate radiation response in different types of tumours, triggering either apoptosis or resistance. However, this complex behaviour has not been studied in brain metastasis. In recent years, we have demonstrated a role of several CAMs during brain metastasis progression. For example, disrupting interactions between circulating tumour cells and brain vasculature using antibodies against ALCAM (CD166) and VLA-4 (α4β1), resulted in a significant decrease in metastatic colonies. Similarly, after LFA-1 (αLβ2) knockdown in tumour cells, brain metastasis growth was greatly reduced. On this basis, the aim of the current study was to determine the effect of concomitant stereotactic brain radiotherapy (SARRP) and anti-CAM treatments in breast cancer brain metastasis in vivo models