ArticleProceedings of the National Academy of Sciences of the United States of America2024
Pharmacological modulation of RB1 activity mitigates resistance to neoadjuvant chemotherapy in locally advanced rectal cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 15 citations in OpenAlex.
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- Cyclin-Dependent Kinases 4 and 6 Inhibitors: An Emerging Therapeutic Framework from Growth Suppression to Tumor Clearance.ACS pharmacology & translational science · 2026Review
- The impactful role of the HDACs in the regulation of gene expression and as targets for disease therapy.Science advances · 2026Review
- Mevalonate pathway rewiring driven by enhancer remodelling confers resistance to KRAS inhibitors in colorectal cancer.Nature communications · 2026Article
- Targeting a super-enhancer induced aldehyde dehydrogenase metabolic loop mitigates CDK4/6 inhibitor resistance in estrogen receptor-positive cancers.Nature communications · 2026Article
- Impact of Neoadjuvant Chemotherapy on Perioperative Tumor Marker Dynamics and Postoperative Recovery in Patients Undergoing Laparoscopic Radical Resection for Rectal Cancer.Journal of gastrointestinal cancer · 2025Article
- Epigenetic synthetic lethality as a cancer therapeutic strategy: synergy of experimental and computational approaches.Epigenomics · 2025Review
- Efficacy of CDK4/6 Inhibition in colorectal cancer and the role of p16 expression in predicting drug resistance.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Cancer gene therapy: historical perspectives, current applications, and future directions.Functional & integrative genomics · 2025Review
- A GRK5 centered prognostic framework for bladder cancer based on palmitoylation and epigenetic regulation.Discover oncology · 2025Article
- Ligustrazine nano-drug delivery system ameliorates doxorubicin-mediated myocardial injury via piezo-type mechanosensitive ion channel component 1-prohibitin 2-mediated mitochondrial quality surveillance.Journal of nanobiotechnology · 2025Article
- Targeting theBiomedicines · 2025Article
- Untangling the Role of MYC in Sarcomas and Its Potential as a Promising Therapeutic Target.International journal of molecular sciences · 2025Review
- Identification of locally advanced rectal cancer-related genes based on transcriptome and mendelian randomization analysis with biological validation.Frontiers in immunology · 2025Article
- 4'-Demethylpodophyllotoxin functions as a mechanism-driven therapy by targeting the PI3K-AKT pathway in Colorectal cancer.Translational oncology · 2025Article
- HDAC-driven mechanisms in anticancer resistance: epigenetics and beyond.Cancer drug resistance (Alhambra, Calif.) · 2024Review
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Authors and funding
27 authors at 4 institutions in 2 countries.
Funding
Abstract
Resistance to neoadjuvant chemotherapy leads to poor prognosis of locally advanced rectal cancer (LARC), representing an unmet clinical need that demands further exploration of therapeutic strategies to improve clinical outcomes. Here, we identified a noncanonical role of RB1 for modulating chromatin activity that contributes to oxaliplatin resistance in colorectal cancer (CRC). We demonstrate that oxaliplatin induces RB1 phosphorylation, which is associated with the resistance to neoadjuvant oxaliplatin-based chemotherapy in LARC. Inhibition of RB1 phosphorylation by CDK4/6 inhibitor results in vulnerability to oxaliplatin in both intrinsic and acquired chemoresistant CRC. Mechanistically, we show that RB1 modulates chromatin activity through the TEAD4/HDAC1 complex to epigenetically suppress the expression of DNA repair genes. Antagonizing RB1 phosphorylation through CDK4/6 inhibition enforces RB1/TEAD4/HDAC1 repressor activity, leading to DNA repair defects, thus sensitizing oxaliplatin treatment in LARC. Our study identifies a RB1 function in regulating chromatin activity through TEAD4/HDAC1. It also provides the combination of CDK4/6 inhibitor with oxaliplatin as a potential synthetic lethality strategy to mitigate oxaliplatin resistance in LARC, whereby phosphorylated RB1/TEAD4 can serve as potential biomarkers to guide the patient stratification.
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Registered trials
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