ReviewJournal of molecular medicine (Berlin, Germany)2016
The molecular mechanism of thalidomide analogs in hematologic malignancies.
Review in Journal of molecular medicine (Berlin, Germany), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05831969 (Lenalidomide to Reverse Drug Resistance After Lenvatinib Combined With PD-1 Inhibitors in the First-line Treatment of Advanced HCC ：a Prospective, Exploratory, Single-arm, Open-label, Multi-center Clinical Study), which is not on this map. Cited by 27 papers.
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.
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.
Lenalidomide to Reverse Drug Resistance After Lenvatinib Combined With PD-1 Inhibitors in the First-line Treatment of Advanced HCC ：a Prospective, Exploratory, Single-arm, Open-label, Multi-center Clinical Study
Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Venetoclax combined with azacitidine in the treatment of secondary myelodysplastic syndrome following multiple myeloma: a case report and literature review.Frontiers in oncology · 2026Article
- Association of hydralazine use with risk of hematologic neoplasms in patients with hypertension: A nationwide population-based cohort study in Taiwan.PLoS medicine · 2025Article
- The Expendables: Overlooked Medications with Anti-Cancer Properties.Current oncology reports · 2025Review
- Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives.International journal of molecular sciences · 2024Review
- Molecular glue degrader for tumor treatment.Frontiers in oncology · 2024Review
- New immunomodulatory anticancer quinazolinone-based thalidomide analogs: design, synthesis and biological evaluation.Future medicinal chemistry · 2024Article
- Design, Synthesis, and Biological Evaluation of New Potential Unusual Modified Anticancer Immunomodulators for Possible Non-Teratogenic Quinazoline-Based Thalidomide Analogs.International journal of molecular sciences · 2023Article
- The Ubiquitin-Proteasome System in Tumor Metabolism.Cancers · 2023Review
- Casein Kinase 1α as a Novel Factor Affects Thyrotropin Synthesis via PKC/ERK/CREB Signaling.International journal of molecular sciences · 2023Article
- IKAROS in Acute Leukemia: A Positive Influencer or a Mean Hater?International journal of molecular sciences · 2023Review
- Phenotypic drug discovery: recent successes, lessons learned and new directions.Nature reviews. Drug discovery · 2022Review
- Design, synthesis, and biological evaluation of novel bioactive thalidomide analogs as anticancer immunomodulatory agents.RSC advances · 2022Article
- Hijacking Host Immunity by the Human T-Cell Leukemia Virus Type-1: Implications for Therapeutic and Preventive Vaccines.Viruses · 2022Review
- Early administration of lenalidomide after allogeneic hematopoietic stem cell transplantation suppresses graft-versus-host disease by inhibiting T-cell migration to the gastrointestinal tract.Immunity, inflammation and disease · 2022Article
- Tumor Microenvironment in Acute Myeloid Leukemia: Adjusting Niches.Frontiers in immunology · 2022Review
- Novel Molecular Mechanism of Lenalidomide in Myeloid Malignancies Independent of Deletion of Chromosome 5q.Cancers · 2021Review
- Potential Role of Pleural Fluid Cytokine Profile in Myelomatous Pleural Effusions.OncoTargets and therapy · 2021Article
- Overcoming cancer therapeutic bottleneck by drug repurposing.Signal transduction and targeted therapy · 2020Review
- Role of HTLV-1 orf-I encoded proteins in viral transmission and persistence.Retrovirology · 2019Review
- Enzymatic Logic of Ubiquitin Chain Assembly.Frontiers in physiology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thalidomide was sold in the 1950s as a sedative and was also used by pregnant women to treat morning sickness. It became notorious for causing severe birth defects and was removed from the market. More than four decades later, thalidomide had a renaissance in the treatment of cancer. Thalidomide and its more potent analogs, lenalidomide and pomalidomide, are nowadays approved treatments for multiple myeloma and myelodysplastic syndrome with deletion of chromosome 5q. In addition, thalidomide and its analogs inhibit release of tumor necrosis factor-α and increase interleukin-2 (IL-2) and interferon-γ release from T cells. The underlying molecular mechanisms for these pleiotropic effects remained obscure until the identification of the cereblon (CRBN) E3 ubiquitin ligase as the primary target of thalidomide and its analogs in 2010. Binding of thalidomide or lenalidomide increases the affinity of CRBN to the transcription factors IKZF1 and IKZF3 and casein kinase 1α (CK1α). Ubiquitination and degradation of these neo-substrates results in IL-2 release and growth arrest of multiple myeloma and MDS cells. The discovery of this previously undescribed mechanism for an approved drug provides a proof-of-concept for the development of new therapeutics that exploit ubiquitin ligases for specific degradation of disease-associated proteins.
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Registered trials
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.