Increased in vivo efficacy of lenalidomide by addition of piroctone olamine

It was recently confirmed that the antifungal agent ciclopirox olamine inhibits Wnt/beta catenin signaling in myeloma. Piroctone olamine (PO) has very similar chemical features to ciclopirox olamine. This study investigated the antitumor effect of PO in vitro and in vivo in a murine myeloma model. PO demonstrated a major apoptotic activity in various human and murine myeloma and lymphoma cell lines, as well as in human primary cells. In vivo, tumor growth, as well as overall survival, was significantly reduced in mice treated with PO as compared to untreated mice. Interestingly, concerning tumor growth and survival of the animals, a significant additive effect was seen by the combination of lenalidomide plus PO as compared to single application. These results reveal a significant selective induction of apoptosis by PO and suggest a significant in vivo effect against myeloma.