Evidence map›Paper›PMID 42158938›Full record

ReviewFrontiers in pharmacology2026

Targeting the proteasome in cancer therapy: development and future opportunities in natural products.

Xiu Zhao, Shanshan Liu, Xinrui Zeng, Yu Liao, Mao Zhang, Qiang Wang, Dan Zhang, Qifeng Chen, Miao Xian, Yong Qin

Abstract readReview
In one paragraph

Review in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Xiu Zhao *Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu, China.
Shanshan Liu *Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu, China.
Xinrui ZengKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu, China.
Yu LiaoKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu, China.
Mao ZhangKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu, China.
Qiang WangCenter for Translational Research in Hematological Malignancies, Houston Methodist Neal Cancer Center, Houston Methodist Academic Institute, Houston, TX, United States.
Dan ZhangKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu, China.
Qifeng ChenKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu, China.
Miao XianKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu, China.
Yong QinKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: The 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. Method: This 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. Results: In 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. Conclusion: The 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.

Indexed as

cancer therapydrug resistancemultiple myelomanatural productproteasome inhibitor

Identifiers

PMID42158938
PMCPMC13180746

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.