Date Published: August 2, 2012
Publisher: Hindawi Publishing Corporation
Author(s): Roberta Martiniani, Valentina Di Loreto, Chiara Di Sano, Alessandra Lombardo, Anna Marina Liberati.
Lenalidomide is a synthetic compound derived by modifying the chemical structure of thalidomide. It belongs to the second generation of immunomodulatory drugs (IMiDs) and possesses pleiotropic properties. Even if lenalidomide has been shown to be active in the treatment of several hematologic malignancies, this review article is mostly focalized on its mode of action in multiple myeloma. The present paper is about the direct and indirect antitumor effects of lenalidomide on malignant plasmacells, bone marrow microenvironment, bone resorption and host’s immune response. The molecular mechanisms and targets of lenalidomide remain largely unknown, but recent evidence shows cereblon (CRBN) as a possible mediator of its therapeutical effects.
Lenalidomide and pomalidomide are synthetic compounds derived by modifying the chemical structure of thalidomide . In particular, as shown in Figure 1, lenalidomide has been synthesized from the structural bone of thalidomide molecule. Lenalidomide has been developed by adding an amino group (NH2–) at 4th position of phthaloyl ring and by removing the carbonyl group (C=O) of the 4-amino-substituted phthaloyl ring. This drug is the result of the pressing need to develop molecules with enhanced immunomodulatory and antitumor activity in comparison to thalidomide. Lenalidomide, which possesses pleiotropic properties, belongs to the second generation of immunomodulatory drugs (IMiDs).
To understand the therapeutic activity of lenalidomide in MM, the knowledge of the pathophysiology of this disease and the complex crosstalk between malignant plasma cells (PCs) and their microenvironment in tumor growth and progression is relevant. In addition, the notion that survival of neoplastic cells is dependent on the escape from the host’s antitumor immune response can help to explain the therapeutic role of lenalidomide.
IMiDs including lenalidomide have proven therapeutically effective molecules in several malignant diseases characterized by different hystogenetic origin of neoplastic cells, as well as by distinct phatogenetic pathways. Notwithstanding these differences IMiDs activity in the diverse neoplasia can be traced back to the pleiotropic mechanism of these molecules.