Table 1.
List of useful drugs for targeting desmoplastic reaction-mediators.
| Drug | Refs | Effects |
|---|---|---|
| All trans-retinoic acid (ATRA) | [100,101,102] | ATRA inhibits the activation of stellate cells. |
| Pirfenidone | [103,104,105,106,107,108,109,110,111,112,113,114,115] | Inhibits collagen fibrils assembly; downregulates the intercellular adhesion molecule-1 (ICAM1); decreases the transformation grow factor beta (TGFβ) at the translational level; down-regulates the pro-fibrotic hedgehog signaling pathway; decreases fibroblast proliferation; blocks myofibroblast differentiation; suppresses tumor necrosis factor alpha (TNFα); decreases cell migration-inducing and hyaluronan-binding proteins. |
| Candesartan | [116] | Angiotensin II receptor inhibitor, which consequently leads to the reduction in stellate cell proliferation. |
| Olmesartan | [29] | Angiotensin II receptor inhibitor, which consequently leads to the reduction in stellate cell proliferation. |
| Saridegib (IPI-926) | [98,117,118] | Hedgehog signaling inhibition. |
| Vismodegib | [119] | Hedgehog signaling inhibition. |
| 4-methyl umbelliferone (4MU) | [85,86,120] | Inhibition of hyaluronan synthase, decreases hyaluronan synthesis; Synergistic activity with gemcitabine. |
| Curcumin | [121,122,123,124] | Inhibits activation of stellate cells. |
| L49H37 a curcumin synthetic analog | [125] | Stellate cell inhibitor. |
| Rhein (natural anthraquinone derivative) | [126,127] | Anti-fibrotic action in PDAC. Reduces collagen I and fibronectin. |
| Resveratrol | [128] | Impedes stellate cell activation by downregulating miRNA 21. This miRNA is also a participant in gemcitabine resistance. |
| Emodin | [129,130,131,132] | Emodin has a wide spectrum of activities related with anti-cancer effects and anti-fibrotic actions. |
| Ellagic acid | [133] | Inhibits the activation and proliferation of stellate cells. |
| Imatinib | [134,135,136,137,138,139,140,141] | Imatinib is anti-fibrotic in pulmonary-induced fibrosis by bleomycin. It is also anti-fibrotic in breast cancer and the liver. However, in a clinical trial of imatinib associated with gemcitabine it did not show any benefits. |
| Metformin | [142,143] | Suppresses desmoplasia by activating AMPK and enhances gemcitabine chemosensitivity. |
| Halofuginone | [144] | Halofuginone is an analog of quinazolinone that shows strong anti-fibrotic properties in an experimental PDAC model. It inhibits the activation of stellate cells. |
| Pegylated recombinant human hyaluronidase | [145] | Acts by enzymatic degradation of hyaluronate. This device can incorporate chemo drugs including checkpoint inhibitors. Research is ongoing. |
| Fasudil priming before chemotherapy | [146,147,148,149,150] | Fasudil is a Rho kinase inhibitor. Administered before chemotherapy it decreased stromal density allowing a better level of drug at the tumor. |
| Pentoxiphyllin | [151,152,153] | Pentoxiphyllin is a reducer of blood viscosity and cytokine production, including TNFα, IL-6, and IL-8 with anti-inflammatory effects and with clear anti-fibrotic effects. |
| Dasatinib | [154] | Dasatinib decreased pancreatic fibrosis in an experimental model of pancreatitis. |