ArticleNature communications2022
Proteomic profiling reveals CDK6 upregulation as a targetable resistance mechanism for lenalidomide in multiple myeloma.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 64 citations in OpenAlex.
- Activating RARβ to overcome immunomodulatory drug resistance in t(4;14) human myeloma.Leukemia · 2026Article
- Understanding and addressing resistance to IMiDs immunomodulatory compounds in multiple myeloma.The FEBS journal · 2026Review
- PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.Innovation (Cambridge (Mass.)) · 2026Review
- The Art of Domesticating Proteins: How Cancer Cells Adapt to Therapeutic and Environmental Stressors.International journal of molecular sciences · 2026Review
- Mechanisms and intervention strategies of microenvironment-mediated drug resistance in multiple myeloma.Cancer cell international · 2026Review
- Multi-omics analysis and functional validation reveal the oncogenic role of TRIP13.Frontiers in immunology · 2026Article
- Circulating extracellular vesicle isomiR signatures predict therapy response in patients with multiple myeloma.Cell reports. Medicine · 2025Article
- Distinct Allosteric Networks in CDK4 and CDK6 in the Cell Cycle and in Drug Resistance.Journal of molecular biology · 2025Article
- Expanding the druggable zinc-finger proteome defines properties of drug-induced degradation.Molecular cell · 2025Article
- DNA-Templated Spatially Controlled Proteolysis Targeting Chimera for Cyclin D1-CDK4/6 Complex Protein Degradation.Journal of the American Chemical Society · 2025Article
- Targeting CDKs in cancer therapy: advances in PROTACs and molecular glues.NPJ precision oncology · 2025Review
- Preclinical and first-in-human of purinostat mesylate, a novel selective HDAC I/IIb inhibitor, in relapsed/refractory multiple myeloma and lymphoma.Signal transduction and targeted therapy · 2025Article
- Resistance to immunomodulatory drugs in multiple myeloma: the cereblon pathway and beyond.Haematologica · 2025Review
- Forcing Ahead: Second-Line Treatment Options for Lenalidomide-Refractory Multiple Myeloma.Cancers · 2025Review
- YY1-induced transcription of AKR1C3 activates the Hedgehog signalling pathway to enhance lenalidomide resistance and glycolytic activity in multiple myeloma cells.Clinical and experimental medicine · 2025Article
- Progress of immune senescence in multiple myeloma treatment resistance.Discover oncology · 2025Review
- Article
- Unlocking the therapeutic potential of selective CDK7 and BRD4 inhibition against multiple myeloma cell growth.Haematologica · 2025Article
- Increased CSN5 expression enhances the sensitivity to lenalidomide in multiple myeloma cells.iScience · 2024Article
- Hyperphenylalaninemia and serotonin deficiency in Dnajc12-deficient mice.Communications biology · 2024Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide are highly effective treatments for multiple myeloma. However, virtually all patients eventually relapse due to acquired drug resistance with resistance-causing genetic alterations being found only in a small subset of cases. To identify non-genetic mechanisms of drug resistance, we here perform integrated global quantitative tandem mass tag (TMT)-based proteomic and phosphoproteomic analyses and RNA sequencing in five paired pre-treatment and relapse samples from multiple myeloma patients. These analyses reveal a CDK6-governed protein resistance signature that includes myeloma high-risk factors such as TRIP13 and RRM1. Overexpression of CDK6 in multiple myeloma cell lines reduces sensitivity to IMiDs while CDK6 inhibition by palbociclib or CDK6 degradation by proteolysis targeting chimeras (PROTACs) is highly synergistic with IMiDs in vitro and in vivo. This work identifies CDK6 upregulation as a druggable target in IMiD-resistant multiple myeloma and highlights the use of proteomic studies to uncover non-genetic resistance mechanisms in cancer.
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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.