Proposed molecular and cellular targets of lenalidomide with potential relevance to human neoplasia. Lenalidomide's biologic effects include alteration of tumor cells' progression through the cell cycle, changes in the marrow microenvironment including disruption of the stem cell niche and inhibition of angiogenesis, variation in levels of inflammatory mediators and cytokines, and modification of immune cell subsets and immunologic activity. The most speculative of these mechanisms at present is perturbation of the DNA damage response, but recent studies have shown that lenalidomide treatment of multiple myeloma is associated with phosphorylation of p53, and expansion of p53-mutant clones may occur during treatment of lower-risk MDS. Modified from Kotla et al.11 Professional illustration by Paulette Dennis.
