Retinoid Treatment for Oral Leukoplakia: Current Evidence and Future Development

Figure 2

Potential synergistic pathways of retinoid resistance. Retinoid resistance may be related to (1) stem accumulation of OLK epithelial cells, (2) decreased production of endogenous retinoids or low retinoids concentrations in target cells, (3) increased retinoids efflux, (4) increased degradation of retinoids, (5) low CRABP-II/FABP5 ratio, (6) epigenetic changes (e.g., DNA hypermethylation and repressive histone modifications), (7) mutations in retinoid-related receptors, (8) changes in posttranslational modification (e.g., abnormal phosphorylation), and (9) cofactors alterations.