Fig. 1.

Possible mechanisms of retinoid resistance. Cancer cell retinoid resistance may be caused by several independent mechanisms including (1) decreased retinoid uptake; (2) intracellular retinoid metabolism; (3) altered intracellular retinoid availability due to CRAB protein binding; (4) increased retinoid efflux by ABC transporters; (5) increased retinoid catabolism catalyzed by cytochrome P450; (6) decreased RAR and/or RXR expression; (7) inhibited retinoid-induced transcription by the repressor complex, (8) altered coactivator structure, expression, or activity; (9) altered downstream target gene expression