Mechanism of immunomodulatory drugs' action in the treatment of multiple myeloma

Abstract

Although immunomodulatory drugs (IMiDs), such as thalidomide, lenalidomide, and pomalidomide, are widely used in the treatment of multiple myeloma (MM), the molecular mechanism of IMiDs' action is largely unknown. In this review, we will summarize recent advances in the application of IMiDs in MM cancer treatment as well as their effects on immunomodulatory activities, anti-angiogenic activities, intervention of cell surface adhesion molecules between myeloma cells and bone marrow stromal cells, anti-inflammatory activities, anti-proliferation, pro-apoptotic effects, cell cycle arrest, and inhibition of cell migration and metastasis. In addition, the potential IMiDs' target protein, IMiDs' target protein's functional role, and the potential molecular mechanisms of IMiDs resistance will be discussed. We wish, by presentation of our naive discussion, that this review article will facilitate further investigation in these fields.

Immunomodulatory drugs and their therapeutic effect in hematological malignancies through cereblon

“…IMiDs are a potent co-stimulator of primary human T cells, synergizing with stimulation via T-cell receptor complex to increase IL-2-mediated T-cell proliferation and interferon gamma (IFN-γ) production [12][13][14][48][49][50]. Secretion of IL-2 and IFN-γ increases the number of natural killer (NK) cells, improves their function and mediates lysis of MM cells (Figure 2).…”

Life‐threatening bowel perforation while on thalidomide‐based triplet regimen for multiple myeloma: a retrospective case series

“…As a result, it is currently recommended as first‐line treatment in both transplant–eligible and –ineligible patients (Bird et al , ). The mechanisms by which thalidomide exerts its anti‐myeloma effects are thought to include a combination of immunomodulation, anti‐angiogenesis and pro‐apoptotic effects (Chang et al , ). Given this broad range of actions, other organ systems can also be targeted, resulting in adverse effects.…”

Novel therapeutic targets in myeloma bone disease

“…As seen in Figure 1, the interaction of myeloma cells with the BM microenvironment enhances myeloma cell growth and survival. IMiDs have been reported to prevent the adhesion of myeloma cells to non-myeloma cells in the BM microenvironment including BMSCs, osteoclasts and immune cells (reviewed in Chang et al, 2013). This would interfere with the vicious cycle of myeloma, reducing myeloma-induced osteoclastogenesis and the resultant growth factors released from bone destruction.…”