ArticleGut2018
Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer.
Article in Gut, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Germline Variants and Risk for Pancreatic Cancer: A Systematic Review and Emerging Concepts.Pancreas · 2018Pooled it
- βIII-tubulin can act as a brake on extrinsic apoptosis in pancreatic cancer.Cell death & disease · 2026Article
- GOT1 Inhibition Induces Extracellular Matrix Remodeling in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Integration of Whole-Genome Sequencing Analysis with Unique Patient-Derived Models Reveals Clinically Relevant Drug Targets in TFCP2 Fusion-Defined Rhabdomyosarcoma.Molecular cancer therapeutics · 2025Article
- Article
- Improving outcomes of patients with pancreatic cancer.Nature reviews. Clinical oncology · 2025Review
- Blood-based biomarkers in pancreatic ductal adenocarcinoma: developments over the last decade and what holds for the future- a review.Frontiers in oncology · 2025Review
- Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response.Science advances · 2024Article
- Palbociclib inhibits the progression of head and neck cancer and improves the Cetuximab response under specific condition in vitro and in vivo.Molecular biology reports · 2024Article
- Pharmacological modulation of RB1 activity mitigates resistance to neoadjuvant chemotherapy in locally advanced rectal cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A stumbling block in pancreatic cancer treatment: drug resistance signaling networks.Frontiers in cell and developmental biology · 2024Review
- Role of neoadjuvant therapy for nonmetastatic pancreatic cancer: Current evidence and future perspectives.World journal of gastrointestinal oncology · 2023Review
- Recent advances in targeted therapy for pancreatic adenocarcinoma.World journal of gastrointestinal oncology · 2023Review
- Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments.Molecular cancer · 2023Review
- Review
- SETD4 Confers Cancer Stem Cell Chemoresistance in Nonsmall Cell Lung Cancer Patients via the Epigenetic Regulation of Cellular Quiescence.Stem cells international · 2023Article
- CDKs Functional Analysis in Low Proliferating Early-Stage Pancreatic Ductal Adenocarcinoma.Journal of bioinformatics and systems biology : Open access · 2023Article
- Applications and mechanisms of the cyclin-dependent kinase 4/6 inhibitor, PD-0332991, in solid tumors.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- A CRISPR Path to Finding Vulnerabilities and Solving Drug Resistance: Targeting the Diverse Cancer Landscape and Its Ecosystem.Advanced genetics (Hoboken, N.J.) · 2022Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
33 authors at 8 institutions in 2 countries.
Funding
Abstract
objectiveExtensive molecular heterogeneity of pancreatic ductal adenocarcinoma (PDA), few effective therapies and high mortality make this disease a prime model for advancing development of tailored therapies. The p16-cyclin D-cyclin-dependent kinase 4/6-retinoblastoma (RB) protein (CDK4) pathway, regulator of cell proliferation, is deregulated in PDA. Our aim was to develop a novel personalised treatment strategy for PDA based on targeting CDK4.
designSensitivity to potent CDK4/6 inhibitor PD-0332991 (palbociclib) was correlated to protein and genomic data in 19 primary patient-derived PDA lines to identify biomarkers of response. In vivo efficacy of PD-0332991 and combination therapies was determined in subcutaneous, intrasplenic and orthotopic tumour models derived from genome-sequenced patient specimens and genetically engineered model. Mechanistically, monotherapy and combination therapy were investigated in the context of tumour cell and extracellular matrix (ECM) signalling. Prognostic relevance of companion biomarker, RB protein, was evaluated and validated in independent PDA patient cohorts (>500 specimens).
resultsSubtype-specific in vivo efficacy of PD-0332991-based therapy was for the first time observed at multiple stages of PDA progression: primary tumour growth, recurrence (second-line therapy) and metastatic setting and may potentially be guided by a simple biomarker (RB protein). PD-0332991 significantly disrupted surrounding ECM organisation, leading to increased quiescence, apoptosis, improved chemosensitivity, decreased invasion, metastatic spread and PDA progression in vivo. RB protein is prevalent in primary operable and metastatic PDA and may present a promising predictive biomarker to guide this therapeutic approach.
conclusionThis study demonstrates the promise of CDK4 inhibition in PDA over standard therapy when applied in a molecular subtype-specific context.
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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.