Table 2.
Selected classes of existing/potential WNT-based drugs in the treatment of NSCLC.
| Agents | Classes | Targets | Pharmacological Mechanisms | Stage of Development | References |
|---|---|---|---|---|---|
| LGK974 | Specific small molecules | ↓PORCN | PORCN inhibitor; inhibits the progression of NSCLC in vitro and in vivo; prolongs the survival time of mice with advanced LUAD | Phase 1 | [134, 135] |
| ETC-159 | |||||
| CGX1321 | |||||
| RXC004 | |||||
| XAV939 | ↓TNKS | Stabilizes AXIN to promote the degradation of β-catenin; inhibits the proliferation and migration of NSCLC cells; improves the effect of cisplatin; enhances the sensitivity of EGFR-mutated NSCLC cells to EGFR-TKIs through the combination of XAV939 and EGFR-TKIs | Discovery | [138, 139, 162] | |
| AZ1366 | |||||
| GDK100017 | ↓WNT2 | Inhibits the canonical WNT signaling; suppresses the proliferation of NSCLC cells; enhances the sensitivity of NSCLC cells to radiotherapy | Discovery | [61, 138, 142] | |
| ICG-001 | ↓β-catenin/CBP | Reduces the transcriptional activation effect of β-catenin/TCF; inhibits the proliferation and invasion of NSCLC cells by abolishing the upregulating effect of BCAT1 | Phase 1 | [143] | |
| Procaine | Anesthetic drug | ↑WIF-1 |
Reactivates WIF-1 from a previously silenced Methylation in NSCLC cells; downregulates the WNT canonical pathway; induces the autophagy and apoptosis of NSCLC cells |
Discovery | [148] |
| Procainamide | Arrhythmic drug | ||||
| OMP-18R5 | Monoclonal antibody | ↓FZD7 | Competitors of WNTs; blocks the activation of the canonical WNT pathway; inhibits the growth of NSCLC cells in vitro and in vivo | Phase 1 | [136, 137, 163] |
| OMP-54F28 | Decoy Receptor | ↓Multiple WNTs | |||
| Curcumin | Plant-based agents | ↓MAT1/WNT/β-catenin | Inhibits the proliferation and invasion of NSCLC cells; induces G0/G1 phase arrest | Phase 1 | [144, 164] |
| 25-OH-PPD | ↓β-catenin/ Cyclin D1/ c-Myc | Inhibits the growth of xenograft tumors in mice; decreases the expression levels of β-catenin and its downstream targets Cyclin D1, CDK4, and c-Myc in lung cancer cells | Discovery | [145] | |
| BDMC | ↑WIF-1 | Inhibits TGF-β1-induced EMT in highly metastatic lung cancer cells | [149] | ||
| Trifluoperazine | Antipsychotic agent | ↓canonical WNT signaling | Inhibits the drug resistance of lung CSCs | Discovery | [151, 159, 160] |
| HY1-Pt | CK2 inhibitor | ||||
| Garcinol | Plant-based agent |
↑/↓ increase/decrease expression level or activity, BDMC bisdemethoxycurcumin, CBP CREB-binding protein, CK2 casein kinase 2, EGFR-TKIs epidermal growth factor receptor-tyrosine kinase inhibitors, EMT epithelial-mesenchymal transition, FZD frizzled, LUAD lung adenocarcinoma, MAT1 metastasis-associated protein 1, NSCLC non-small cell lung cancer, PORCN porcupine, TCF T-cell factor, TGF-β1 transforming growth factor beta 1, TNKS tankyrases, WIF-1 WNT inhibitory factor 1, 25-OH-PPD 25-hydroxyprotopanaxadiol