NEW YORKResearchers at Weill Cornell Medical College are
investigating retinoic acid in the hope of extending its use in
cancer chemoprevention as well as chemotherapy. Various vitamin A
derivatives have already been shown to be useful in reversing
premalignant changes such as leukoplakia and in treating
Retinoic acid is the most biologically potent of the retinoids,
a master regulator of cell growth and differentiation, Lorraine
Gudas, PhD, professor of pharmacology, said at a media briefing
sponsored by Weill Cornell.
Dr. Gudas explained that when a normal cell is bathed in a vitamin A
medium, retinol is converted for storage as a retinyl ester. It is
also converted into various metabolites, of which retinoic acid is
only one. Retinoic acid zeroes in on the cell nucleus, where it binds
to receptors (RAR and RXR) and is active in upreg-ulation of various
genes. Three different types of proteins (alpha, beta, and gamma)
have been identified for both RAR and RXR, she said.
Tumor cells do not store vitamin A. The enzyme LRAT is not
expressed so it cannot produce retinyl esters, Dr. Gudas said.
Her laboratory, in collaboration with Dr. David Nanus, found, for
example, that normal kidney tissue had more than 10 times as much
retinyl esters as renal tumor tissue from the same patient.
Tumor cells are profoundly vitamin A deficient, which is why
normal growth and differentiation do not occur, she said.
Treating this vitamin A deficiency, she noted, may lead
to effective anticancer therapy. The challenge is to devise a
delivery method for retinol that will overcome tumor cell resistance
to retinol storage. One approach, she said, involves coating retinyl
esters with a liposomal cover and injecting them directly into tumor