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Exosomes in multiple myeloma: from bench to bedside
Abstract:
Multiple myeloma (MM) remains an incurable plasma cell malignancy that develops in the bone marrow (BM). This BM is partially responsible for protecting the MM cells against current standard-of-care therapies and for accommodating MM-related symptoms such as bone resorption and immune suppression. Increasing evidence has implicated extracellular vesicles (EV), including exosomes in the different processes within the BM. Exosomes are <150-nm-sized vesicles secreted by different cell types including MM cells. These vesicles contain protein and RNA cargo that they deliver to the recipient cell. In this way, they have been implicated in MM-related processes including osteolysis, angiogenesis, immune suppression, and drug resistance. Targeting exosome secretion could therefore potentially block these different processes. In this review, we will summarize the current findings of exosome-related processes in the BM and describe not only the current treatment strategies to counter them but also how exosomes can be harnessed to deliver toxic payloads. Finally, an overview of the different clinical studies that investigate EV cargo as potential MM biomarkers in liquid biopsies will be discussed.
Insights
Multiple myeloma (MM) is an incurable cancer where exosomes in bone marrow promote disease progression. Targeting these exosomes offers new therapeutic strategies and potential biomarkers for early detection.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Multiple myeloma (MM) is an incurable plasma cell malignancy originating in the bone marrow (BM).
- The BM microenvironment protects MM cells and drives disease symptoms like bone resorption and immune suppression.
- Extracellular vesicles (EVs), particularly exosomes, play a significant role in MM progression within the BM.
Approach:
- This review summarizes the role of exosomes in MM-related processes within the BM.
- It discusses current therapeutic strategies targeting exosome secretion.
- It explores the potential of using exosomes as drug delivery vehicles and biomarkers.
Key Points:
- Exosomes secreted by MM cells carry protein and RNA cargo, influencing osteolysis, angiogenesis, immune suppression, and drug resistance.
- Targeting exosome secretion is a potential therapeutic strategy to inhibit MM progression.
- Exosomes can be engineered to deliver toxic payloads to MM cells.
- EV cargo in liquid biopsies shows promise as a biomarker for MM detection and monitoring.
Conclusions:
- Exosomes are critical mediators of the bone marrow microenvironment in multiple myeloma.
- Targeting exosome pathways presents novel therapeutic opportunities for MM.
- Exosome-derived biomarkers hold potential for non-invasive MM diagnostics and prognostics.
