PGP and neoplasm: In addition to the biochemical modifications using the ligand to RMT, structural refinement of drugs to diminish their affinity to AETs at the BBB/BBTB greatly contributes to their brain entry, given that a number of anti-tumor drugs especially molecularly targeted agents have proven substrate liability for both P-gp (ABCB1) and BCRP (ABCG2) (Oberoi et al., 2016).