SRS has been shown to extend survival in these cases, though melanoma and renal cell carcinoma are known to be particularly radioresistant.115 Tumor resistance to systemic therapy is often attributed to obstruction and active exclusion by the BBB, in particular, p-glycoprotein (ABCB1) mediated efflux.116–118 However, interactions within the TME have also been shown to play important roles in BrM chemoresistance. This evidence concerns the gene ABCB1 and hereditary clear cell renal cell carcinoma.