Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Antonio Giovanni Solimando
* ,
Matteo Claudio Da Vià
ORCID logo ,
Sebastiano Cicco
,
Patrizia Leone
ORCID logo ,
Giuseppe Di Lernia
,
Donato Giannico
,
Vanessa Desantis
,
Maria Antonia Frassanito
,
Arcangelo Morizio
,
Julia Delgado Tascon
,
Giuseppe Ranieri
,
Roberto Ria
ORCID logo ,
Leo Rasche
,
K. Martin Kortüm
,
Andreas Beilhack
,
Vito Racanelli
ORCID logo ,
Angelo Vacca
,
Hermann Einsele
Version 1 : Received: 15 June 2019 / Approved: 16 June 2019 / Online: 16 June 2019 (10:05:40 CEST)

A peer-reviewed article of this Preprint also exists.

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. 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.

Abstract

Multiple myeloma (MM) is a genetically heterogenous disease that includes a subgroup of 10-15% of patients facing dismal survival despite most intensive treatment. The aim of this review article is to provide an integrated clinical and biological overview on the high-risk MM discussing the novel therapeutic perspectives aimed to target 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 high-risk profile and refractoriness to therapy. Among the current clinical difficulties in MM, patient’s management manipulating the tumor niche represents a major challenge given the limited knowledge about the MM-milieu interaction. The angiogenesis and bystander infiltrate constitute pivotal mechanisms of 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. Therefore, it would be worth to better select the population and the MM stage that could profit to a dual immune/vasculogenesis targeting. The comprehensive knowledge of the genetic heterogeneity and MM high-risk ecosystem enforce a systematic bench-to-bedside approach. Despite significant improvements in the biology knowledge, MM is still a chronic and incurable neoplasia and therapeutic options able to overcome the relapsing/refractory behavior represent an unmet clinical need. Here, we corroborate previous biological findings providing a synthetic outlook of novel druggable targets. We also summarize the existing multi-omics-based risk profiling tools, in order to better personalize the patient-oriented clinical management.

Keywords

multiple myeloma; angiogenesis; extramedullary disease; drug resistance; bone marrow microenvironment.

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.