Retinoic Acids in the Treatment of Most Lethal Solid Cancers

Although the use of oral administration of pharmacological all-trans retinoic acid (ATRA) concentration in acute promyelocytic leukaemia (APL) patients was approved for over 20 years and used as standard therapy still to date, the same use in solid cancers is still controversial. In the present review the literature about the top five lethal solid cancers (lung, stomach, liver, breast, and colon cancer), as defined by The Global Cancer Observatory of World Health Organization, and retinoic acids (ATRA, 9-cis retinoic acid, and 13-cis retinoic acid, RA) was compared. The action of retinoic acids in inhibiting the cell proliferation was found in several cell pathways and compartments: from membrane and cytoplasmic signaling, to metabolic enzymes, to gene expression. However, in parallel in the most aggressive phenotypes several escape routes have evolved conferring retinoic acids-resistance. The comparison between different solid cancer types pointed out that for some cancer types several information are still lacking. Moreover, even though some pathways and escape routes are the same between the cancer types, sometimes they can differently respond to retinoic acid therapy, so that generalization cannot be made. Further studies on molecular pathways are needed to perform combinatorial trials that allow overcoming retinoic acids resistance.4n