ArticleNature communications2024
MYC induces CDK4/6 inhibitors resistance by promoting pRB1 degradation.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The trial behind it
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Who cites it
31 citing papers in PubMed, 29 citations in OpenAlex.
- Biomarkers of response to neoadjuvant palbociclib plus anastrozole in endocrine-resistant estrogen receptor-positive/HER2-negative breast cancer: a phase 2 trial.Nature communications · 2026Trial
- A scalable, high-throughput glue perturbation screening platform for molecular glue discovery.iScience · 2026Article
- A noncanonical function of the tyrosine degradation enzyme FAH drives CDK4/6 inhibitor resistance in breast cancer.Science advances · 2026Article
- Mapping malignant T-cell states and immune circuits in Sézary syndrome by single-cell analysis.Journal of the European Academy of Dermatology and Venereology : JEADV · 2026Article
- Molecular signatures of triple-negative breast cancer cells acquiring palbociclib resistance via continuous exposure.Oncology letters · 2026Article
- Integrated Bioinformatics and Experimental Validation of Post-Translational Modification-Related Biomarkers in Myocardial Ischemia-Reperfusion Injury.Journal of cardiovascular translational research · 2026Article
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- MYC in Oncogenesis and Therapeutic Implications.MedComm · 2026Review
- Molecular modulators of cyclin-dependent kinase 4/6 inhibitor response in experimental glioma identified through genome-wide CRISPR-Cas9 screening.Neuro-oncology · 2026Article
- Lethal clinical outcome and immuno-fibrotic contexture in refractory urothelial carcinoma harboring MYC amplification and overexpression.British journal of cancer · 2026Article
- Alternative Splicing in Cyclin-Dependent Kinase 4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer.Drug development research · 2026Review
- Evolving First-Line Endocrine Therapy in HR+/HER2- Metastatic Breast Cancer: CDK4/6 Inhibition, Biomarker-Guided Strategies and Emerging Therapeutic Paradigms.Current oncology (Toronto, Ont.) · 2026Review
- MKRN2-Mediated Degradation of IGF2BP3 Suppresses MYC and Enhances CDK4/6 Inhibitor Sensitivity in Bladder Cancer.Cancers · 2026Article
- Comparative analysis of distinct genomic landscapes in young-onset gBRCA1/2 breast cancer.JCI insight · 2026Article
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- Sec8: a novel positive regulator of RIG-I in anti-RNA viral defense.Cell death & disease · 2026Article
- Genome-wide screenings identify BAP1 as a synthetic-lethality target with CDK4/6 inhibitors.Science advances · 2026Article
- Metformin sensitizes non-small cell lung cancer to CDK4/6 inhibitor treatment by reducing lysosomal trapping.Science China. Life sciences · 2026Article
- Personalized ctDNA detection and genomic profiling in the NeoRHEA Study.NPJ breast cancer · 2025Article
- Research progress on the role of AGC kinase family in bladder cancer.Discover oncology · 2025Review
Corrections and comments
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Authors and funding
22 authors at 3 institutions in 3 countries.
Funding
Abstract
CDK4/6 inhibitors (CDK4/6i) show anticancer activity in certain human malignancies, such as breast cancer. However, their application to other tumor types and intrinsic resistance mechanisms are still unclear. Here, we demonstrate that MYC amplification confers resistance to CDK4/6i in bladder, prostate and breast cancer cells. Mechanistically, MYC binds to the promoter of the E3 ubiquitin ligase KLHL42 and enhances its transcription, leading to RB1 deficiency by inducing both phosphorylated and total pRB1 ubiquitination and degradation. We identify a compound that degrades MYC, A80.2HCl, which induces MYC degradation at nanomolar concentrations, restores pRB1 protein levels and re-establish sensitivity of MYC high-expressing cancer cells to CDK4/6i. The combination of CDK4/6i and A80.2HCl result in marked regression in tumor growth in vivo. Altogether, these results reveal the molecular mechanisms underlying MYC-induced resistance to CDK4/6i and suggest the utilization of the MYC degrading molecule A80.2HCl to potentiate the therapeutic efficacy of CDK4/6i.
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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.