ArticleJournal of experimental & clinical cancer research : CR2021
Regorafenib enhances anti-PD1 immunotherapy efficacy in murine colorectal cancers and their combination prevents tumor regrowth.
Article in Journal of experimental & clinical cancer research : CR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 2 of them syntheses that pooled it.
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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
67 citing papers in PubMed, 2 syntheses or guidelines pooled it, 108 citations in OpenAlex.
- The efficacy and safety of regorafenib/fruquintinib combined with PD-1/PD-L1 for metastatic colorectal cancer: a meta-analysis based on single-arm studies.Frontiers in immunology · 2025Pooled it
- Research hotspots and frontiers in the tumor microenvironment of colorectal cancer: a bibliometric study from 2014 to 2024.Frontiers in oncology · 2025Pooled it
- Regorafenib plus modified gemcitabine-oxaliplatin in patients with advanced biliary tract cancer. The randomized phase Ib/II BREGO study.The oncologist · 2025Trial
- Phase 2 Trial of Regorafenib in Recurrent/Metastatic Adenoid Cystic Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- First-line regorafenib with nivolumab and chemotherapy in advanced oesophageal, gastric, or gastro-oesophageal junction cancer in the USA: a single-arm, single-centre, phase 2 trial.The Lancet. Oncology · 2023Trial
- FGFR pathway inhibition enhances PD-1 blockade and modulates antitumor immunity in colorectal cancer models.BMC cancer · 2026Article
- [Novel therapeutic strategies for liver metastases driven by the common microenvironment].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Dihydroartemisinin inhibits mutant KRAS to potentiate regorafenib plus anti-PD-1 in KRAS-mutant colorectal cancer liver metastases.Cell death & disease · 2026Article
- Enhancing Immunotherapeutic Response in Colorectal Cancer with a Neuropilin 1-Targeting Tumor-Penetrating Peptide.Cancer research communications · 2026Article
- Unlocking Wnt's weak spot: Glycosylated nanoalbumins to reignite immune responses in MSS-CRC.Journal of pharmaceutical analysis · 2026Article
- Baseline Tumor Features and Systemic Immune Dynamics Underlying Efficacy in MSS Metastatic Colorectal Cancer Treated with Regorafenib, Ipilimumab, and Nivolumab.Cancer immunology research · 2026Article
- Research progress of small molecule protein kinase inhibitors (SMKIs) in the treatment of colorectal cancer: mechanism, application, and future prospects.Frontiers in pharmacology · 2026Review
- Parasite in cancer therapy: molecular mechanisms and translational potential.Frontiers in immunology · 2026Review
- Review
- The immunosurveillance signature predicts the prognosis and immunotherapy sensitivity for colon adenocarcinoma.Scientific reports · 2025Article
- The phosphatase CTDSPL2 promotes proliferation, invasion, metastasis and regorafenib resistance in osteosarcoma.Journal of bone oncology · 2025Article
- Regulation and Function of Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): The Role of the SRIF System in Macrophage Regulation.International journal of molecular sciences · 2025Review
- Enhancing Colorectal Cancer Treatment Through VEGF/VEGFR Inhibitors and Immunotherapy.Current treatment options in oncology · 2025Review
- From silent partners to potential therapeutic targets: macrophages in colorectal cancer.Cancer immunology, immunotherapy : CII · 2025Review
- Stanniocalcin 1 in Patients with Refractory Colorectal Cancer Treated with Regorafenib: A Post Hoc Biomarker Analysis of the TEXCAN and CORRECT Trials.Cancer research communications · 2025Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPatients with advanced colorectal cancer (CRC) have a poor prognosis. Combinations of immunotherapies and anti-angiogenic agents are currently being evaluated in clinical trials. In this study, the multikinase inhibitor regorafenib (REG) was combined with an anti-programmed cell death protein 1 (aPD1) antibody in syngeneic murine microsatellite-stable (MSS) CT26 and hypermutated MC38 colon cancer models to gain mechanistic insights into potential drug synergism.
methodsGrowth and progression of orthotopic CT26 and subcutaneous MC38 colon cancers were studied under treatment with varying doses of REG and aPD1 alone or in combination. Sustained effects were studied after treatment discontinuation. Changes in the tumor microenvironment were assessed by dynamic contrast-enhanced MRI, and histological and molecular analyses.
resultsIn both models, REG and aPD1 combination therapy significantly improved anti-tumor activity compared with single agents. However, in the CT26 model, the additive benefit of aPD1 only became apparent after treatment cessation. The combination treatment efficiently prevented tumor regrowth and completely suppressed liver metastasis, whereas the anti-tumorigenic effects of REG alone were abrogated soon after drug discontinuation. During treatment, REG significantly reduced the infiltration of immunosuppressive macrophages and regulatory T (Treg) cells into the tumor microenvironment. aPD1 significantly enhanced intratumoral IFNγ levels. The drugs synergized to induce sustained M1 polarization and durable reduction of Treg cells, which can explain the sustained tumor suppression.
conclusionsThis study highlights the synergistic immunomodulatory effects of REG and aPD1 combination therapy in mediating a sustained inhibition of colon cancer regrowth, strongly warranting clinical evaluation in CRC, including MSS tumors.
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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.