IMiDs induce pleiotropic anti-cancer effects
- 37 Downloads
Lenalidomide (Revlimid®, also known as CC-5013) and pomalidomide (CC-4047) are IMiDs and chemical derivatives of thalidomide. Lenalidomide was introduced in 2004 and is currently approved for treatment of multiple myeloma and 5q-myelodysplastic syndromes (MDS). In addition, IMiDs are currently tested in a wide variety of haematological as well as solid tumours. IMiDs have three main anti-tumour properties, i.e. a direct anti-tumour effect, an inhibitory/modulatory effect on the tumour stroma/microenvironment supporting growth and survival of tumour cells including anti-angiogenic properties as well as a very potent immunomodulatory effect. The latter includes activation of T, NK and NKT cells as well as modulation of the function of mononuclear cells (DC and monocytes). However, the exact anti-cancer mechanisms of IMiDs in vivo remain elusive so far. This brief review will focus on the current concepts explaining the anti-cancer effects of IMiDs.
KeywordsIMiDs Immune-modulation Tumour stroma Anti-angiogenesis
Unable to display preview. Download preview PDF.
- Galustian C, Meyer B, Labarthe MC, Dredge K, Klaschka D, Henry J, et al. The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol Immunother, 2008Google Scholar
- Lapalombella R, Yu B, Triantafillou G, Liu Q, Butchar JP, Lozanski G, et al. Lenalidomide down-regulates the CD20 antigen and antagonizes direct and antibody-dependent cellular cytotoxicity of rituximab on primary chronic lymphocytic leukemia cells. Blood, 112(13): 5180–5189, 2008PubMedCrossRefGoogle Scholar
- Lu L, Payvandi F, Wu L, Zhang LH, Hariri RJ, Man HW, et al. The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions. Microvasc Res, 2008Google Scholar
- Pellagatti A, Jadersten M, Forsblom AM, Cattan H, Christensson B, Emanuelsson EK, et al. Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q-syndrome patients. Proc Natl Acad Sci USA, 104(27): 11406–11411, 2007PubMedCrossRefGoogle Scholar