Clinical and in vitro Response to 13-cis-Retinoic Acid in Interferon-alpha Resistant Renal Cell Carcinoma

Abstract

Retinoids are known to control many important biological processes, including differentiation, morphogenesis, growth and tissue homeostasis. More recently, clinical and pre-clinical results provide evidence for an antiproliferative effect of 13-cis-retinoic acid (13cRA) in interferon-alpha (IFN-α) treated renal cell carcinoma patients. The manner in which 13cRA augments antitumor effects and modulates biologic and clinical responses of renal cell carcinoma to IFN-α remains elusive. In the present study, we report induction of apoptosis and objective tumor regression in response to 13cRA in advanced renal cell carcinoma patients refractory to IFN-α. Among 21 patients treated there were one complete and four partial remissions (objective response rate, 24%; median response duration 8+ months). Preliminary evidence suggests that 13cRA acid may reverse IFN-α resistance in renal cell carcinoma.