Experimental studies with liarozole (R 75 251): An antitumoral agent which inhibits retinoic acid breakdown

Advances and Trends in Hormonal Therapy for Advanced Prostate Cancer

“…A 60-70% decrease in median tumour volume was seen when R75251 was applied as a dietary admixture. By oral ga vage a 90% reduction in median tumour volume was observed in androgen-independent tumours AT-6 sq (at 60 mg/kg twice daily) [77,78]. In relapsed, hormone-resis tant prostate cancer patients, objective partial responses and subjective responses have been found in almost half of the patients [79].…”

“…Retinoid acid is known to be the key molecule in cellular proliferation and differentiation and has shown anticarcinogenic and antitumoural effects. R75251 enhances, dose-dependently, the retinoid acid concentration in se rum and tumours [78]. Suramin Suramin is a trypanocidal drug which also has a cyto static effect on prostate cancer cell lines [73][74][75], In the human cell lines PC3 and DU145, suramin exerts its cyto static effect by inhibiting the binding of growth factors to cell surface receptors [73].…”

Acquired Resistance to All-Trans Retinoic Acid Therapy in Acute Promyelocytic Leukemia

“…[3,9] In other words, the organism reacts by a feedback mechanism to high and prolon ged doses of ATRA. Induction of specific cytochrome-Pasodependent enzymes have been observed during ATRA treat ment of rodents, and inhibition of these enzymes by ketoconazole or liarozole results in increased plasma ATRA levels [32][33][34]. Recently, the CRABPII has been suggested as a protein linked to the cellular metabolism of ATRA, acting as a transporter to the endoplasmatic reticulum, where ATRA is metabolized.…”

Molecular Diagnostics and Therapy of Prostate Cancer: New Avenues

“…Liarozole was developed as an inhibitor of cytochrome P450-dependent (adrenal) androgen synthesis, but it turned out to be an effective inhibitor of 4-hydroxylase. Nevertheless, differentiation was enhanced by up-regulation of E-cadherin production which in turn induced changes in keratin expression, and there was circumstantial evidence that retinoic acid concentrations increased [13]. An objective response was observed in patients but changes in differentiation probably did not account for all the observed clinical effects and the patient groups were not appropriate.…”