ArticleCell reports2019
Pulsatile MEK Inhibition Improves Anti-tumor Immunity and T Cell Function in Murine Kras Mutant Lung Cancer.
Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
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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
49 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report.Clinical lung cancer · 2020Trial
- Soluble Uric Acid Drives CD8+ T-cell Exhaustion by Inducing KSR1-Mediated MAPK Hyperactivation.Cancer research · 2026Article
- Multi-tyrosine kinase inhibitors: exploring immunomodulatory effects on various immune cell types in cancer.Cancer cell international · 2026Review
- Mechanistic basis and therapeutic modulation of T cell fitness to enhance CAR-T cell efficacy in hematological malignancies.Frontiers in immunology · 2026Review
- Tempered signal strength via low-dose MEK inhibition optimizes therapeutic performance of engineered T cells.Journal for immunotherapy of cancer · 2025Article
- A Phase 1/1B Trial of Pembrolizumab and Trametinib in Advanced NSCLC Enriched for KRAS Mutations.JTO clinical and research reports · 2025Article
- Cellular immunotherapy targeting CLL-1 for juvenile myelomonocytic leukemia.Nature communications · 2025Article
- TGM2 regulated by transcription factor NR3C1 drives p38 MAPK-mediated tumor progression and immune evasion in lung squamous cell carcinoma.Frontiers in immunology · 2025Article
- Serum creatine kinase elevation following tyrosine kinase inhibitor treatment in cancer patients: Symptoms, mechanism, and clinical management.Clinical and translational science · 2024Review
- Stromal reprogramming overcomes resistance to RAS-MAPK inhibition to improve pancreas cancer responses to cytotoxic and immune therapy.Science translational medicine · 2024Article
- Intermittent MEK Inhibition with GITR Costimulation Rescues T-cell Function for Increased Efficacy with CTLA-4 Blockade in Solid Tumor Models.Cancer immunology research · 2024Article
- RAF and MEK Inhibitors in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024Review
- Trametinib sensitizes KRAS-mutant lung adenocarcinoma tumors to PD-1/PD-L1 axis blockade via Id1 downregulation.Molecular cancer · 2024Article
- Targeting MEK in non-small cell lung cancer.Current problems in cancer · 2024Review
- BRAF - a tumour-agnostic drug target with lineage-specific dependencies.Nature reviews. Clinical oncology · 2024Review
- APR-246 increases tumor antigenicity independent of p53.Life science alliance · 2024Article
- Mediating kinase activity in Ras-mutant cancer: potential for an individualised approach?Frontiers in pharmacology · 2024Review
- Facts and Hopes on RAS Inhibitors and Cancer Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Prognostic Factors and Markers in Non-Small Cell Lung Cancer: Recent Progress and Future Challenges.Genes · 2023Review
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
KRAS is one of the driver oncogenes in non-small-cell lung cancer (NSCLC) but remains refractory to current modalities of targeted pathway inhibition, which include inhibiting downstream kinase MEK to circumvent KRAS activation. Here, we show that pulsatile, rather than continuous, treatment with MEK inhibitors (MEKis) maintains T cell activation and enables their proliferation. Two MEKis, selumetinib and trametinib, induce T cell activation with increased CTLA-4 expression and, to a lesser extent, PD-1 expression on T cells in vivo after cyclical pulsatile MEKi treatment. In addition, the pulsatile dosing schedule alone shows superior anti-tumor effects and delays the emergence of drug resistance. Furthermore, pulsatile MEKi treatment combined with CTLA-4 blockade prolongs survival in mice bearing tumors with mutant Kras. Our results set the foundation and show the importance of a combinatorial therapeutic strategy using pulsatile targeted therapy together with immunotherapy to optimally enhance tumor delay and promote long-term anti-tumor immunity.
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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.