Anti-Angiogenic Activity of Drugs in Multiple Myeloma.

Simple Summary: The "angiogenic switch" contributes to the transition from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM), sustaining disease progression and drug resistance. In this review, we describe the anti-angiogenic activity of drugs employed in clinical settings for the management of MM patients providing important information on their pharmacological profile and on the molecular mechanisms responsible for their direct and indirect anti-angiogenic effect. Angiogenesis represents a pivotal hallmark of multiple myeloma (MM) that correlates to patients' prognosis, overall survival, and drug resistance. Hence, several anti-angiogenic drugs that directly target angiogenic cytokines (i.e., monoclonal antibodies, recombinant molecules) or their cognate receptors (i.e., tyrosine kinase inhibitors) have been developed. Additionally, many standard antimyeloma drugs currently used in clinical practice (i.e., immunomodulatory drugs, bisphosphonates, proteasome inhibitors, alkylating agents, glucocorticoids) show anti-angiogenic effects further supporting the importance of inhibiting angiogenesis from potentiating the antimyeloma activity. Here, we review the most important anti-angiogenic therapies used for the management of MM patients with a particular focus on their pharmacological profile and on their anti-angiogenic effect in vitro and in vivo. Despite the promising perspective, the direct targeting of angiogenic cytokines/receptors did not show a great efficacy in MM patients, suggesting the need to a deeper knowledge of the BM angiogenic niche for the design of novel multi-targeting anti-angiogenic therapies. [ABSTRACT FROM AUTHOR]