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Pomalidomide is an oral immunomodulatory agent that, as demonstrated in vitro, inhibits proliferation and induces apoptosis of tumor cells, and inhibits proliferation of lenalidomide-resistant myeloma cells.1-3
In preclinical studies, pomalidomide has demonstrated direct tumoricidal and immunomodulatory effects, which are mediated in both myeloma and immune cells by co-opting cereblon, a component of the E3 ubiquitin ligase complex.1-5?This redirection triggers proteasomal degradation of the transcription factors Ikaros and Aiolos,3,5,6?resulting in downregulation of the myeloma survival signals IRF4 and c-Myc and upregulation of the immunoregulatory molecule IL-2.1,5,6?Additionally, pomalidomide may have inhibitory effects on stromal-cell support in the bone marrow microenvironment, including inhibition of soluble protein production that supports myeloma cell growth and angiogenesis4,7
Pomalidomide Hypothesized Mechanism of Action
Pomalidomide is an IMiD?agent hypothesized to have tumoricidal and immunomodulatory effects in multiple myeloma.