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Open AccessReview

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

1
Department of Internal Medicine II, University Hospital, 97080 Würzburg, Germany
2
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine “G. Baccelli”, University of Bari Medical School, 70124 Bari, Italy
3
Orthopedics and Traumatology Unit ASL BA-Ospedale della Murgia “Fabio Perinei”, 70022 Altamura, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2019, 8(7), 997; https://doi.org/10.3390/jcm8070997
Received: 15 June 2019 / Revised: 27 June 2019 / Accepted: 29 June 2019 / Published: 9 July 2019
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. View Full-Text
Keywords: multiple myeloma; angiogenesis; extramedullary disease; drug resistance; bone marrow microenvironment multiple myeloma; angiogenesis; extramedullary disease; drug resistance; bone marrow microenvironment
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Solimando, A.G.; Da Vià, M.C.; Cicco, S.; Leone, P.; Di Lernia, G.; Giannico, D.; Desantis, V.; Frassanito, M.A.; Morizio, A.; Delgado Tascon, J.; Melaccio, A.; Saltarella, I.; Ranieri, G.; Ria, R.; Rasche, L.; Kortüm, K.M.; Beilhack, A.; Racanelli, V.; Vacca, A.; Einsele, H. High-Risk Multiple Myeloma: Integrated Clinical and Omics Approach Dissects the Neoplastic Clone and the Tumor Microenvironment. J. Clin. Med. 2019, 8, 997.

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