ArticleOncogene2019
Cell cycle plasticity driven by MTOR signaling: integral resistance to CDK4/6 inhibition in patient-derived models of pancreatic cancer.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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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.
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Who cites it
41 citing papers in PubMed.
- Trial
- Emerging Strategies to Inhibit the G1/S Transition for Cancer Therapy.Cancer research · 2026Review
- Targeting a super-enhancer induced aldehyde dehydrogenase metabolic loop mitigates CDK4/6 inhibitor resistance in estrogen receptor-positive cancers.Nature communications · 2026Article
- Case Report: Acquired CDKN2A/B deletion and mTOR inhibitor resistance in TSC2-mutant metastatic epithelioid angiomyolipoma.Frontiers in medicine · 2026Article
- Proteomics in pancreatic cancer.Biomarker research · 2025Review
- Discrete vulnerability to pharmacological CDK2 inhibition is governed by heterogeneity of the cancer cell cycle.Nature communications · 2025Article
- Cell Cycle Plasticity and Heterogeneity: An Underappreciated Feature of Cancer and Treatment Response.Cancer heterogeneity and plasticity · 2025Article
- gdGSE: An algorithm to evaluate pathway enrichment by discretizing gene expression values.Computational and structural biotechnology journal · 2025Article
- Separable Cell Cycle Arrest and Immune Response Elicited through Pharmacological CDK4/6 and MEK Inhibition in RASmut Disease Models.Molecular cancer therapeutics · 2024Article
- Synergistic Efficacy of CDK4/6 Inhibitor Abemaciclib and HDAC Inhibitor Panobinostat in Pancreatic Cancer Cells.Cancers · 2024Article
- The Extracellular Niche and Tumor Microenvironment Enhance KRAS Inhibitor Efficacy in Pancreatic Cancer.Cancer research · 2024Article
- Copy Number Variations in Pancreatic Cancer: From Biological Significance to Clinical Utility.International journal of molecular sciences · 2023Review
- Article
- PROTAC-mediated CDK degradation differentially impacts cancer cell cycles due to heterogeneity in kinase dependencies.British journal of cancer · 2023Article
- miR-30e-5p-mediated FOXD1 promotes cell proliferation by blocking cellular senescence and apoptosis through p21/CDK2/Rb signaling in head and neck carcinoma.Cell death discovery · 2023Article
- Review
- CDK4 phosphorylation status and rational use for combining CDK4/6 and BRAF/MEK inhibition in advanced thyroid carcinomas.Frontiers in endocrinology · 2023Article
- Noncoding RNAs: an emerging modulator of drug resistance in pancreatic cancer.Frontiers in cell and developmental biology · 2023Review
- Cancer cell cycle dystopia: heterogeneity, plasticity, and therapy.Trends in cancer · 2022Review
- RB loss determines selective resistance and novel vulnerabilities in ER-positive breast cancer models.Oncogene · 2022Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC), like many KRAS-driven tumors, preferentially loses CDKN2A that encodes an endogenous CDK4/6 inhibitor to bypass the RB-mediated cell cycle suppression. Analysis of a panel of patient-derived cell lines and matched xenografts indicated that many pancreatic cancers have intrinsic resistance to CDK4/6 inhibition that is not due to any established mechanism or published biomarker. Rather, there is a KRAS-dependent rapid adaptive response that leads to the upregulation of cyclin proteins, which participate in functional complexes to mediate resistance. In vivo, the degree of response is associated with the suppression of a gene expression signature that is strongly prognostic in pancreatic cancer. Resistance is associated with an adaptive gene expression signature that is common to multiple kinase inhibitors, but is attenuated with MTOR inhibitors. Combination treatment with MTOR and CDK4/6 inhibitors had potent activity across a large number of patient-derived models of PDAC underscoring the potential clinical efficacy.
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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.