Table 1.
Leptin as a potential target of the novel therapeutic strategies for breast cancer treatment.
| Therapeutic strategy level | Mechanism of therapy |
|---|---|
| Leptin antagonists96 | Mouse and human leptin antagonists (D23L/L39A/D40A/F41A) exhibited more than 60-fold increased binding to leptin receptor |
| Leptin peptide receptor antagonist28 | Inhibition of leptin signaling via leptin peptide receptor antagonists simultaneously decreased the levels of VEGF/VEGFR2, IL-1, and Notch |
| Leptin-antagonist97 | Leptin-antagonist Honokiol (HNK) inhibits leptin-induced epithelial-mesenchymal-transition and mammosphere-formation along with a reduction in the expression of stemness factors, Oct4 and Nanog, and increase miR-34a |
| Inflammasome activation42 | Block NLRC4 inflammasome activation or IL-1β signaling transduction. which drives disease progression through adipocyte-mediated vascular endothelial growth factor A expression |
| JAK/STAT3-regulated fatty acid β-oxidation pathway97 | Inhibiting JAK/STAT3 blocks breast cancer stem cell self-renewal and expression of diverse lipid metabolic genes, including carnitine palmitoyltransferase 1B which encodes the critical enzyme for fatty acid β-oxidation |
| Inhibiting leptin signaling80 | Synthetic FXR (regulator of the cross talk between breast cancer cells and cancer-associated fibroblasts) agonist GW4064 affects the tumor-promoting activities of cancer-associated fibroblasts in breast malignancy |
| Notch signaling pathway98 | Targeting different molecules along in Notch signaling pathway includes a variety of γ-secretase inhibitors antibodies against Notch1-3 receptors or DLL4 ligand |
| Insulinlike growth factor 1 and insulinlike growth factor 1 receptor58 | Targeting IGF-1/IGF-1R axis in several pathophysiological aspects of breast cancer microenvironment and cancer stemness |
| Leptin receptor antagonist92 | Selective leptin receptor antagonist, peptide LDFI (Leu-Asp-Phe-Ile), abrogated leptin effects on Tsg101 expression and on exosome secretion in breast cancer cells |
| Inflammasome41 | Inhibition of the inflammasome by treatment with a pharmacological inhibitor of caspase 1 or gene silencing of NLRP3 |