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Potential for all-trans retinoic acid [tretinoin] to enhance interferon-alpha treatment response in chronic myelogenous leukemia, melanoma, myeloma, and renal cell carcinoma

This note mechanistically accounts for recent unexplained findings that all-trans retinoic acid [ATRA, also termed tretinoin] exerts an anti-viral effect against hepatitis C virus [HCV] in chronically infected patients, in whom ATRA also showed synergy with interferon-alpha. How HCV replication was suppressed was unclear. Both effects of ATRA can be accounted for by ATRA's upregulation of RIG protein, an 18 kDa product of retinoic induced gene-1. Increased RIG then couples ATRA to increased Type 1 interferons' production. Details of this mechanism predict that ATRA will similarly augment interferon-alpha activity in treating chronic myelogenous leukemia, melanoma, myeloma, and renal cell carcinoma and that the addition of ribavirin and/or bexarotene will each incrementally enhance interferon-alpha responses in these cancers.