Narrative review explores natural products targeting proteasome in multiple myeloma

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Frontiers in Medicine Published May 4, 2026 Medically reviewed May 4, 2026 DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider natural product-derived proteasome inhibitors as a potential avenue to address resistance in multiple myeloma, though clinical data are lacking.

This is a narrative review summarizing the literature up to 2025 on natural products that directly target the proteasome or enhance cellular sensitivity to proteasome inhibitors in multiple myeloma. The authors discuss various natural product-derived compounds, including marizomib, and their mechanisms of action.

Key findings are qualitative, as no pooled effect sizes are reported. The review suggests that natural product-derived proteasome inhibitors hold significant potential for developing next-generation therapies that can overcome resistance and improve clinical outcomes.

A major limitation acknowledged by the authors is that primary and acquired resistance remain a major challenge in the treatment of multiple myeloma. The review does not provide specific data on efficacy, safety, or comparative effectiveness.

For clinicians, this review offers a broad overview of emerging natural product-based strategies, but practice relevance is limited by the lack of primary data and the narrative nature of the synthesis. Further clinical studies are needed to validate these approaches.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

BackgroundThe ubiquitin–proteasome pathway is a critical therapeutic target in malignancies, particularly multiple myeloma. The development of proteasome inhibitors (PIs) has marked a milestone in multiple myeloma therapy and now constitutes the backbone of frontline treatment regimens. However, primary and acquired resistance remain a major challenge, underscoring the need to identify new PIs as well as agents that can resensitize resistant cells.MethodThis review provides an overview of the current clinical applications of PIs and offers a comprehensive summary of natural products that either directly target the proteasome or enhance cellular sensitivity to PIs. Relevant clinical trials and literature published up to 2025 were retrieved from PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov, focusing on the biological and pharmacological activities, structure-activity relationships, and clinical outcomes.ResultsIn this review, we summarize the current clinical applications of PIs and specifically highlight the discovery of natural products that directly target the proteasome or enhance cellular sensitivity to PIs. We also discuss the clinical progress of marizomib, the only natural product-derived PI, that has advanced to clinical trials. Despite existing challenges, natural product-derived PIs hold significant potential for the development of next-generation therapies that can overcome resistance and improve clinical outcomes.ConclusionThe development of novel natural product-derived PIs and rational combination strategies offers promising opportunities for overcoming resistance in cancer therapy. Although challenges remain, the remarkable structural diversity of natural products provides a rich reservoir for drug discovery, underscoring the importance of continued exploration and innovation in this field.