ArticleNature communications2021
Proteomics of resistance to Notch1 inhibition in acute lymphoblastic leukemia reveals targetable kinase signatures.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
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Who cites it
25 citing papers in PubMed.
- CREB1 and GSK3 Isoforms as Potential Adaptive Signaling Nodes in PI3K/Akt/mTOR Inhibitor Treated Philadelphia Chromosome-Positive B-ALL.International journal of molecular sciences · 2026Article
- NUDT21 Drives T-Cell Acute Lymphoblastic Leukemia Through Dual Regulation of Alternative Polyadenylation and Transcriptional Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multi-omics analyses reveal novel metabolic signatures of post-traumatic deep vein thrombosis in patients with coronary heart disease.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- PKC isoforms in hematopoietic lineages and myeloid/lymphoid leukemias: mechanistic insights and therapeutic prospects.Frontiers in oncology · 2026Review
- Advancing cancer research: Cutting-edge insights from colorectal cancer patient-derived xenograft mouse models.Genes & diseases · 2026Review
- Phosphoproteomics of osimertinib-tolerant persister cells reveals targetable kinase-substrate signatures.Molecular systems biology · 2025Article
- Transcriptional Control of TSPAN32 in T-ALL Reveals Interplay Between TAL1 and NOTCH1.Biomedicines · 2025Article
- A ROS-Responsive Dual-Targeting Drug Nanocarrier Serving as a GSI Synergist and Ferroptosis Sensitizer for T-Cell Acute Lymphoblastic Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Notch Inhibitors and BH3 Mimetics in T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2024Review
- Integrated landscape of plasma metabolism and proteome of patients with post-traumatic deep vein thrombosis.Nature communications · 2024Article
- µPhos: a scalable and sensitive platform for high-dimensional phosphoproteomics.Molecular systems biology · 2024Article
- Metabolic Profiling as an Approach to Differentiate T-Cell Acute Lymphoblastic Leukemia Cell Lines Belonging to the Same Genetic Subgroup.International journal of molecular sciences · 2024Article
- Novel research and future prospects of artificial intelligence in cancer diagnosis and treatment.Journal of hematology & oncology · 2023Review
- Notch Signaling in Health and Disease.International journal of molecular sciences · 2023Article
- Resistance mechanism to Notch inhibition and combination therapy in human T-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- Patient-derived xenograft models in cancer therapy: technologies and applications.Signal transduction and targeted therapy · 2023Review
- Mass Spectrometry-Based Proteomics Workflows in Cancer Research: The Relevance of Choosing the Right Steps.Cancers · 2023Review
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- Editorial: Plant-based bioactive compounds: natural tumor prevention?Frontiers in nutrition · 2023Article
- An oncogene addiction phosphorylation signature and its derived scores inform tumor responsiveness to targeted therapies.Cellular and molecular life sciences : CMLS · 2022Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch1 is a crucial oncogenic driver in T-cell acute lymphoblastic leukemia (T-ALL), making it an attractive therapeutic target. However, the success of targeted therapy using γ-secretase inhibitors (GSIs), small molecules blocking Notch cleavage and subsequent activation, has been limited due to development of resistance, thus restricting its clinical efficacy. Here, we systematically compare GSI resistant and sensitive cell states by quantitative mass spectrometry-based phosphoproteomics, using complementary models of resistance, including T-ALL patient-derived xenografts (PDX) models. Our datasets reveal common mechanisms of GSI resistance, including a distinct kinase signature that involves protein kinase C delta. We demonstrate that the PKC inhibitor sotrastaurin enhances the anti-leukemic activity of GSI in PDX models and completely abrogates the development of acquired GSI resistance in vitro. Overall, we highlight the potential of proteomics to dissect alterations in cellular signaling and identify druggable pathways in cancer.
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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 Socratic graph.