ArticleGut2021
Targeting dual signalling pathways in concert with immune checkpoints for the treatment of pancreatic cancer.
Article in Gut, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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
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
52 citing papers in PubMed, 87 citations in OpenAlex.
- Trial
- CDK4/6-targeted therapy for gastrointestinal cancers: from resistance mechanisms to immuno-combination strategies guided by biomarkers.Frontiers in immunology · 2026Review
- AC005034.3/hsa-miR-126-5p/EIF3H axis: bioinformatics analysis, expression validation, and association with prognosis and immunosuppressive microenvironment in pancreatic adenocarcinoma.Frontiers in cell and developmental biology · 2026Article
- The Dual Effects of CDK4/6 Inhibitors on Tumor Immunity.Cancers · 2025Review
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
- Acquired resistance in cancer: towards targeted therapeutic strategies.Nature reviews. Cancer · 2025Review
- Drugging the 'undruggable' KRAS: breakthroughs, challenges, and opportunities in pancreatic cancer.Cancer biology & medicine · 2025Review
- Article
- Resistance mechanisms and therapeutic strategies of CDK4 and CDK6 kinase targeting in cancer.Nature cancer · 2025Review
- Cell Cycle Plasticity and Heterogeneity: An Underappreciated Feature of Cancer and Treatment Response.Cancer heterogeneity and plasticity · 2025Article
- Separable Cell Cycle Arrest and Immune Response Elicited through Pharmacological CDK4/6 and MEK Inhibition in RASmut Disease Models.Molecular cancer therapeutics · 2024Article
- Identification of three subtypes of ovarian cancer and construction of prognostic models based on immune-related genes.Journal of ovarian research · 2024Article
- Nanoparticle delivery of innate immune agonists combined with senescence-inducing agents promotes T cell control of pancreatic cancer.Science translational medicine · 2024Article
- Injectable hybrid hydrogels enable enhanced combination chemotherapy and roused anti-tumor immunity in the synergistic treatment of pancreatic ductal adenocarcinoma.Journal of nanobiotechnology · 2024Article
- Combinatorial strategies to target RAS-driven cancers.Nature reviews. Cancer · 2024Review
- The Extracellular Niche and Tumor Microenvironment Enhance KRAS Inhibitor Efficacy in Pancreatic Cancer.Cancer research · 2024Article
- Activation of endogenous retroviruses and induction of viral mimicry by MEK1/2 inhibition in pancreatic cancer.Science advances · 2024Article
- Tumor immune microenvironment-based therapies in pancreatic ductal adenocarcinoma: time to update the concept.Journal of experimental & clinical cancer research : CR · 2024Review
- Targeting KRAS mutations in pancreatic cancer: opportunities for future strategies.Frontiers in medicine · 2024Review
- PROTAC-mediated CDK degradation differentially impacts cancer cell cycles due to heterogeneity in kinase dependencies.British journal of cancer · 2023Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveThis study exploits the intersection between molecular-targeted therapies and immune-checkpoint inhibition to define new means to treat pancreatic cancer.
designPatient-derived cell lines and xenograft models were used to define the response to CDK4/6 and MEK inhibition in the tumour compartment. Impacts relative to immunotherapy were performed using subcutaneous and orthotopic syngeneic models. Single-cell RNA sequencing and multispectral imaging were employed to delineate effects on the immunological milieu in the tumour microenvironment.
resultsWe found that combination treatment with MEK and CDK4/6 inhibitors was effective across a broad range of PDX models in delaying tumour progression. These effects were associated with stable cell-cycle arrest, as well as the induction of multiple genes associated with interferon response and antigen presentation in an RB-dependent fashion. Using single-cell sequencing and complementary approaches, we found that the combination of CDK4/6 and MEK inhibition had a significant impact on increasing T-cell infiltration and altering myeloid populations, while potently cooperating with immune checkpoint inhibitors.
conclusionsTogether, these data indicate that there are canonical and non-canonical features of CDK4/6 and MEK inhibition that impact on the tumour and immune microenvironment. This combination-targeted treatment can promote robust tumour control in combination with immune checkpoint inhibitor therapy.
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What OpenQuestion holds
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.