ArticleNature cancer2024
Targeted activation of ferroptosis in colorectal cancer via LGR4 targeting overcomes acquired drug resistance.
Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 81 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- ATM is associated with the prognosis of colorectal cancer: a systematic review.Frontiers in oncology · 2025Pooled it
- Redox-manipulating nanocarriers for anticancer drug delivery: a systematic review.Journal of nanobiotechnology · 2024Pooled it
- DDR1 sustains ferroptosis resistance in pancreatic ductal adenocarcinoma via SLC40A1-mediated iron homeostasis.Oncogene · 2026Article
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- A fungal-derived benzothiazole derivative overcomes osimertinib resistance in NSCLC by targeting SCD1.Natural products and bioprospecting · 2026Article
- CAF-derived exosomes inhibit ferroptosis via GALNT14-mediated O-GalNAcylation of SLC7A11 in colorectal cancer.Oncogene · 2026Article
- Target FADS1-arachidonic acid-ferroptosis axis: A metabolic bridge linking matrix stiffness to PDAC stemness.Materials today. Bio · 2026Article
- METTL3/FTO drives ferroptosis in colorectal cancer by targeting mJournal of gastroenterology · 2026Article
- Ferroptosis in colorectal cancer: Molecular mechanisms and regulatory crosstalk with therapeutic prospects (Review).Oncology reports · 2026Review
- 'Student Geng' ignites research-integrity scandal in China after calling out senior academics.Nature · 2026Article
- Cholesterol-depleting nanozyme amplifies membrane-diffusive ferroptosis for potentiating anti-tumor immunity in colorectal cancer.Journal of materials science. Materials in medicine · 2026Article
- miR-29a-3p regulates SPARC to inhibit ferroptosis and promote cell proliferation in gastric cancer.Scientific reports · 2026Article
- Translating ferroptosis into oncology: challenges, opportunities and future directions.Nature reviews. Clinical oncology · 2026Review
- LGR5: from stem cell marker to therapeutic target.Trends in cancer · 2026Review
- Targeting HIF-1α promotes ferroptosis and boosts antitumor immunity in MSS colorectal cancer.Redox biology · 2026Article
- H4K8 lactylation-mediated ferroptosis defense drives EGFR-TKI resistance in lung adenocarcinoma.Apoptosis : an international journal on programmed cell death · 2026Article
- LRP2-mediated regulation of ferroptosis through the Wnt/β-catenin-GPX4 axis in colorectal cancer liver metastasis and chemoresistance.Cell death discovery · 2026Article
- Regulatory mechanisms of LGR4 on cancer and cancer stem cell properties.Discover oncology · 2026Review
- Bufalin Suppresses Pancreatic Ductal Adenocarcinoma Through ER Stress-Ferroptosis Crosstalk Associated with IPInternational journal of molecular sciences · 2026Article
- Organoids in cancer therapy: translational applications and clinical promise.Molecular cancer · 2026Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retracted
Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
Abstract
Acquired drug resistance is a major challenge for cancer therapy and is the leading cause of cancer mortality; however, the mechanisms of drug resistance are diverse and the strategy to specifically target drug-resistant cancer cells remains an unmet clinical issue. Here, we established a colorectal cancer-derived organoid biobank and induced acquired drug resistance by repeated low-level exposures of chemo-agents. Chemosensitivity profiling and transcriptomic analysis studies revealed that chemoresistant cancer-derived organoids exhibited elevated expression of LGR4 and activation of the Wnt signaling pathway. Further, we generated a monoclonal antibody (LGR4-mAb) that potently inhibited LGR4-Wnt signaling and found that treatment with LGR4-mAb notably sensitized drug-induced ferroptosis. Mechanistically, LGR4-dependent Wnt signaling transcriptionally upregulated SLC7A11, a key inhibitor of ferroptosis, to confer acquired drug resistance. Our findings reveal that targeting of Wnt signaling by LGR4-mAb augments ferroptosis when co-administrated with chemotherapeutic agents, demonstrating a potential opportunity to fight refractory and recurrent cancers.
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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.