Table 3.
Drugs, physical methods of cure, and natural drugs used to decrease tumor interstitial fluid pressure (TIFP), IFF, and VP.
| Drugs | IFP gel phase | IFP solid phase | Human studies | Animal studies | Effects | Reference | CR |
|---|---|---|---|---|---|---|---|
| Angiogenesis inhibitors | |||||||
| Bezacizumab | ↓ | ѵ | VN | Ariffin | + | ||
| Sorafenib | ↓ | ѵ | VN | Ariffin | + | ||
| Imatimib | ↓ | ѵ | Ariffin | + | |||
| Block of receptor-2 | ↓ | ѵ | VN↑Nano ≤12 nm | Chauhan | + | ||
| Vasoactive agents | |||||||
| Hidralazine | ↓ | ѵ | ↓ IFP not correlated to tumor volume | Podobnik | |||
| Hidralazine | ↓ | ѵ | ↑ Oxygenation | Jarm | |||
| Vascular disrupting agents | |||||||
| ZD6126 | Skliarenko | ||||||
| Combretastatin-A4 | ↓ | ѵ | Ley | ||||
| Chemotherapy | |||||||
| Chemo immunotherapy | ↓ | Melanoma lymphoma | ↓ Responders | Curti | |||
| Taxanes | ↓ | ѵ | ↓ | Bronstad | + | ||
| Taxanes | ↓ | ↓ | ѵ | ↓ | Griffon-Etiennie | + | |
| Paclitaxel | ↓ | Breast cancer | ↓ | Taghian | + | ||
| PGE1 | ↓ | ѵ | ↓ | Salnikov | |||
| Dexamethasone | ↓ | ѵ | ↓ | Kristjansen | ++ | ||
| Physical methods | |||||||
| Hyperthermia | ↓ | ѵ | Leunig | ++ | |||
| Hyperthermia | ѵ | ↑ Oxygenation | Sen | ++ | |||
| Hyperthermia | ѵ | ↑ MOABs | Jain M | ++ | |||
| Hyperthermia | ѵ | ↑ Extravasation nanoparticles | Kong | ++ | |||
| Radiotherapy | ↓ | ѵ | ↓ IFP correlated to radiocurability | Rofstad | ++ | ||
| US | ↓ | ѵ | ↑ Gene therapy | Ziadloo Yuh | ++ | ||
| PDT | ↓ | ѵ | ↑ Delivery of liposomial doxorubicin | Perentes | ++ | ||
| PDT | ↓ | ѵ | ↓ IFP time dependent | Leunig et al. (109) | ++ | ||
| Drugs acting on cellular matrix and cell density (CD) | |||||||
| Collegenases | ↓ | ѵ | ↑ MOABs | Eikenes | |||
| Hyaluronidase | ↓ | ѵ | ↑ Liposomal doxorubicin | Eikenes | |||
| Hyaluronidase | ↓ CD | ↑ | Croix | ||||
| Losartan | ↓ | ѵ | Diop- Frimpong | ++ | |||
| TGF-β inhibitors | ↓ | ѵ | ↑ Of chemotherapy/nano drugs delivery | Papageorgis | + | ||
| FAP vaccine | ↓ | ↑ 70% drug uptake | Loffler | ||||
| Natural substances | |||||||
| EGCG | ↓ | ѵ | ↑ Activity cisplatin | Deng | ++ | ||
| ↑ Oxygenation | |||||||
| w-3 FAs | ↓ | ѵ | ↑ Activity of docetaxel | Kornfeld | ++ | ||
| ↓ Activity of vascular NOS | |||||||
| Drugs or physical methods acting on IFF | |||||||
| HT | ↑ C | ѵ | ↑ Nanoparticles extravasation | Kong, Leunig | ++ | ||
| CED | ↑ C | ↑ Convection (bypass of BB) | Saito, | + | |||
| CED | ↑ C | ѵ | Vandergrift | + | |||
| US | ↑ Convection | Frenkel | ++ | ||||
| Angiotensin inhibitors | ↓ FF | ↓ | Chauhan et al. (110) | ++ | |||
| VEGFR-3 | ↓ FF | ↓ Lymphangiogenesis | Tammela | + | |||
| Drugs acting on vascular permeability (VP) | |||||||
| Angiopoietin | ↓ | Gavard | |||||
| Bezacizumab | ↓ | Gerstner, Pishko | |||||
| Notch ligand Delta-like4 | ↓ | Li; Azzi | |||||
BB, blood brain barrier; IFP, interstitial fluid pressure; IFF, interstitial fluid flow; EGCG, epigallocathechin-3-gallate; W-3FAs, omega-3 fatty acids; VN, vascular normalization; CL, capillary leakage; ↓, decrease; ↑, increase; ↑ C, increased convection; CD, cell density; CED, convection enhanced delivery; CR, clinical relevance, + with certain side effects, ++ with scarce side effects; NOS, nitric oxide synthase; MOABs, monoclonal antibodies.