期刊
JOURNAL OF CLINICAL MEDICINE
卷 8, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/jcm8070997
关键词
multiple myeloma; angiogenesis; extramedullary disease; drug resistance; bone marrow microenvironment
资金
- Italian Association for Cancer Research (AIRC) [20441]
- Global Doc Project-Progetto Global Doc (GLOBALDOC) Project [CUP H96J17000160002]
- Action Plan for Cohesion
- German SKELMET/muBone consortium - German Research Council [DFG FOR 1586, SPP 2084]
- Bayerische Forschungsstiftung consortium FortiTher [WP2TP3]
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.
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