Table 1.
Selective biochemical modulation for circumventing the tumor BBB in treating glioma.
| Biochemical Modulation | Tumor Enriched Expression | Applied Drugs | FDA Approved | Tight Junction Effects | Vesicular Transport Effects | Clinical Stage | Refs |
|---|---|---|---|---|---|---|---|
| ATP-sensitive potassium channel (KATP channel) | Yes | Minoxidil sulfate | Yes | Occludin↓, Claudin-5↓ | Transport vesicles↑, Caveolin-1↑ | Preclinical | [57,58,59] |
| Calcium-activated potassium channel (KCa channel) | Yes | NS1619 | No | _ | Transport vesicles↑, Caveolin-1↑ | Preclinical | [60,61,62,63,64,65] |
| Phosphodiesterase 5 (PDE5) | Yes | Vardenafil (Levitra) | Yes | _ | Transport vesicles↑ | Preclinical | [66,67,68,69,70] |
| Bradykinin type 2 receptor (B2R) | Yes | Bradykinin and analogs | No | ZO-1↓, Occludin↓, Claudin-5↓ | Caveolin-1↑ | Clinical | [71,72,73,74,75,76,77,78,79,80,81] |
| Adenosine 2A receptor (A2AR) | Yes | Lexiscan | Yes | Occludin↓, Claudin-5↓ | _ | Clinical | [20,82,83,84,85] |
| Papaverine | _ | _ | No | Occludin↓, Claudin-5↓ | _ | Clinical | [86,87,88,89] |
| microRNAs | _ | miR-132-3p | No | _ | Caveolin-1↑ | Preclinical | [90] |
Note: Up-regulated ↑; Down-regulated ↓.