CyTodiffErEnTia Tion by retinoids a Novel ThErapEuTic Option in Onco Logy RaTionaL Combinations wiTh OThEr ThErapEuTic Agents

Enrico GaraTTini, Maurizio Gianni', anD MinEko TErao

I. Premise and Scope: Differentiation Therapy with

Retinoids Is a Significant Goal in the Management of the Neoplastic Diseases 303 II. The Classical Nuclear RAR Pathway Is Complex and Has Led to the Development of Different Types of Synthetic Retinoids 305

III. Retinoids Promote Differentiation in Numerous Types of Neoplastic Cells 307

IV. Retinoids Exert Pleiotropic Effects Interacting with Multiple Intracellular Pathways: An Opportunity for Combination Therapy 313

V. Retinoid-Based Differentiation Therapy, General Observations, and Conclusion 334 References 336

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