Multiple myeloma (MM) is a genetically heterogeneous disease that includes a subgroup of 10-15% of patients facing dismal survival despite the most intensive treatment. Despite improvements in biological knowledge, MM is still an incurable neoplasia, and therapeutic options able to overcome the relapsing/refractory behavior represent an unmet clinical need. The aim of this review is to provide an integrated clinical and biological overview of high-risk MM, discussing novel therapeutic perspectives, targeting the neoplastic clone and its microenvironment. The dissection of the molecular determinants of the aggressive phenotypes and drug-resistance can foster a better tailored clinical management of the high-risk profile and therapy-refractoriness. Among the current clinical difficulties in MM, patients' management by manipulating the tumor niche represents a major challenge. The angiogenesis and the stromal infiltrate constitute pivotal mechanisms of a mutual collaboration between MM and the non-tumoral counterpart. Immuno-modulatory and anti-angiogenic therapy hold great efficacy, but variable and unpredictable responses in high-risk MM. The comprehensive understanding of the genetic heterogeneity and MM high-risk ecosystem enforce a systematic bench-to-bedside approach. Here, we provide a broad outlook of novel druggable targets. We also summarize the existing multi-omics-based risk profiling tools, in order to better select candidates for dual immune/vasculogenesis targeting.

High-Risk Multiple Myeloma: Integrated Clinical and Omics Approach Dissects the Neoplastic Clone and the Tumor Microenvironment / A.G. Solimando, M.C. Da Vià, S. Cicco, P. Leone, G. Di Lernia, D. Giannico, V. Desantis, M.A. Frassanito, A. Morizio, J. Delgado Tascon, A. Melaccio, I. Saltarella, G. Ranieri, R. Ria, L. Rasche, K.M. Kortüm, A. Beilhack, V. Racanelli, A. Vacca, H. Einsele. - In: JOURNAL OF CLINICAL MEDICINE. - ISSN 2077-0383. - 8:7(2019), pp. 997.1-997.26. [10.3390/jcm8070997]

High-Risk Multiple Myeloma: Integrated Clinical and Omics Approach Dissects the Neoplastic Clone and the Tumor Microenvironment

M.C. Da Vià;
2019

Abstract

Multiple myeloma (MM) is a genetically heterogeneous disease that includes a subgroup of 10-15% of patients facing dismal survival despite the most intensive treatment. Despite improvements in biological knowledge, MM is still an incurable neoplasia, and therapeutic options able to overcome the relapsing/refractory behavior represent an unmet clinical need. The aim of this review is to provide an integrated clinical and biological overview of high-risk MM, discussing novel therapeutic perspectives, targeting the neoplastic clone and its microenvironment. The dissection of the molecular determinants of the aggressive phenotypes and drug-resistance can foster a better tailored clinical management of the high-risk profile and therapy-refractoriness. Among the current clinical difficulties in MM, patients' management by manipulating the tumor niche represents a major challenge. The angiogenesis and the stromal infiltrate constitute pivotal mechanisms of a mutual collaboration between MM and the non-tumoral counterpart. Immuno-modulatory and anti-angiogenic therapy hold great efficacy, but variable and unpredictable responses in high-risk MM. The comprehensive understanding of the genetic heterogeneity and MM high-risk ecosystem enforce a systematic bench-to-bedside approach. Here, we provide a broad outlook of novel druggable targets. We also summarize the existing multi-omics-based risk profiling tools, in order to better select candidates for dual immune/vasculogenesis targeting.
angiogenesis; bone marrow microenvironment; drug resistance; extramedullary disease; multiple myeloma
Settore MED/15 - Malattie del Sangue
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/892441
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