Immunomodulatory drugs (IMiDs) in multiple myeloma: mechanism of action and clinical implications
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Immunomodulatory drugs (IMiDs) are a class of drugs, derived from the teratogenic compound thalidomide, that have made a major impact on treatment of many diseases, from multiple myeloma to assorted inflammatory diseases. From its dark beginnings as a teratogenic agent that caused phocomelia in newborn infants, thalidomide has resurged decades later as a potent immunomodulatory agent with widespread anti-inflammatory and anti-tumor effects. Research examining Thalidomide’s effects in vitro on malignant myeloma cells has led to the development of newer analogs, lenalidomide and pomalidomide, both of which are now available on the market. Clinically, these drugs have had a tremendous impact on patient progression-free survival, especially when administered in conjunction with other novel agents. Despite the numerous properties that have been reported for IMiDs, until recently, little was known about their mechanism of action. Knowledge of likely only one of IMiDs’ direct mechanism of action has not only opened up opportunities for additional discoveries, but also propelled research to better characterize genetic profiles of multiple myeloma patients and potential biomarkers of disease progression and response to treatment. This thesis will attempt to review the history and literature behind the biological mechanisms of IMiDs, the clinical risks and benefits of using such drugs as treatment for cancer, and future directions for areas of research.