Current Trends in ATRA Delivery for Cancer Therapy

Abstract

All-Trans Retinoic Acid (ATRA) is the most active metabolite of vitamin A. It is critically involved in the regulation of multiple processes, such as cell differentiation and apoptosis, by activating specific genomic pathways or by influencing key signaling proteins. Furthermore, mounting evidence highlights the anti-tumor activity of this compound. Notably, oral administration of ATRA is the first choice treatment in Acute Promyelocytic Leukemia (APL) in adults and NeuroBlastoma (NB) in children. Regrettably, the promising results obtained for these diseases have not been translated yet into the clinics for solid tumors. This is mainly due to ATRA-resistance developed by cancer cells and to ineffective delivery and targeting. This up-to-date review deals with recent studies on different ATRA-loaded Drug Delivery Systems (DDSs) development and application on several tumor models. Moreover, patents, pre-clinical, and clinical studies are also reviewed. To sum up, the main aim of this in-depth review is to provide a detailed overview of the several attempts which have been made in the recent years to ameliorate ATRA delivery and targeting in cancer.

The Intimate Relationship among EMT, MET and TME: A T(ransdifferentiation) E(nhancing) M(ix) to Be Exploited for Therapeutic Purposes

“…For example, a differentiation therapy approach using ATRA for the treatment of APL has shown some promise [152], although progressive resistance to monotherapy with ATRA emerges over a relatively short period of time, typically within 3-6 months [152]. This leukemia differentiates into mature granulocytes after ATRA treatment.…”

D-α-Tocopherol-Based Micelles for Successful Encapsulation of Retinoic Acid

“…A selected ATRA-TPGS colloidal suspension was further loaded in a hydrogel matrix, which represents the ideal vehicle for topical drug delivery, both for its feasibility and patient compliance. Indeed, nanocarrier-loaded hydrogels, made of Carbopol ® 980 (carbomer) as the gelling agent, combine the advantages of a standard technology with the improvements offered by nanotechnology [ 28 ]. A comprehensive sketch of the chemical structures and ATRA-TPGS dispersion into the gel polymer network is reported in Figure 1 .…”

Differentiating Neuroblastoma: A Systematic Review of the Retinoic Acid, Its Derivatives, and Synergistic Interactions

“…To overcome those limitations, two approaches are being investigated, using RA compounds in combination treatments ( Table 1 ) and improving RA drug delivery systems (DDS). The use of alternative DDS for differentiation therapy has recently been reviewed in other cancers, such as acute promyelocytic leukaemia (APL) [ 77 ]. Currently, oral administration of RA is the first-choice treatment in neuroblastoma patients.…”