ArticleOncotarget2014
GUCY2C lysosomotropic endocytosis delivers immunotoxin therapy to metastatic colorectal cancer.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 28 citations in OpenAlex.
- Could GUCY2C-targeted pharmacotherapy be effective in treating colorectal cancer?Expert review of clinical pharmacology · 2026Article
- Immunotherapy for precision medicine in colorectal cancer.Expert review of precision medicine and drug development · 2025Article
- CD8α Structural Domains Enhance GUCY2C CAR-T Cell Efficacy.Cancer biology & therapy · 2024Article
- Mechanisms of drug resistance in nutrient-depleted colorectal cancer cells: insights into lysosomal and mitochondrial drug sequestration.Biology open · 2024Review
- Targeting gastrointestinal cancers with chimeric antigen receptor (CAR)-T cell therapy.Cancer biology & therapy · 2022Article
- Chimeric adenoviral (Ad5.F35) and listeria vector prime-boost immunization is safe and effective for cancer immunotherapy.NPJ vaccines · 2022Article
- T-Cell Responses to Immunodominant Listeria Epitopes Limit Vaccine-Directed Responses to the Colorectal Cancer Antigen, Guanylyl Cyclase C.Frontiers in immunology · 2022Article
- Guanylyl cyclase 2C (GUCY2C) in gastrointestinal cancers: recent innovations and therapeutic potential.Expert opinion on therapeutic targets · 2021Review
- Guanylyl cyclase C as a biomarker for immunotherapies for the treatment of gastrointestinal malignancies.Biomarkers in medicine · 2021Review
- GUCY2C as a biomarker to target precision therapies for patients with colorectal cancer.Expert review of precision medicine and drug development · 2021Article
- An update on guanylyl cyclase C in the diagnosis, chemoprevention, and treatment of colorectal cancer.Expert review of clinical pharmacology · 2020Review
- Chimeric Ad5.F35 vector evades anti-adenovirus serotype 5 neutralization opposing GUCY2C-targeted antitumor immunity.Journal for immunotherapy of cancer · 2020Article
- Two distinct GUCY2C circuits with PMV (hypothalamic) and SN/VTA (midbrain) origin.Brain structure & function · 2019Article
- Silencing the GUCA2A-GUCY2C tumor suppressor axis in CIN, serrated, and MSI colorectal neoplasia.Human pathology · 2019Article
- Split tolerance permits safe Ad5-GUCY2C-PADRE vaccine-induced T-cell responses in colon cancer patients.Journal for immunotherapy of cancer · 2019Article
- Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases.Cancer immunology research · 2018Article
- GUCY2C maintains intestinal LGR5Oncotarget · 2017Article
- Review
- Guanylate cyclase C as a target for prevention, detection, and therapy in colorectal cancer.Expert review of clinical pharmacology · 2017Review
- Prime-Boost Immunization Eliminates Metastatic Colorectal Cancer by Producing High-Avidity Effector CD8Journal of immunology (Baltimore, Md. : 1950) · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The emergence of targeted cancer therapy has been limited by the paucity of determinants which are tumor-specific and generally associated with disease, and have cell dynamics which effectively deploy cytotoxic payloads. Guanylyl cyclase C (GUCY2C) may be ideal for targeting because it is normally expressed only in insulated barrier compartments, including intestine and brain, but over-expressed by systemic metastatic colorectal tumors. Here, we reveal that GUCY2C rapidly internalizes from the cell surface to lysosomes in intestinal and colorectal cancer cells. Endocytosis is independent of ligand binding and receptor activation, and is mediated by clathrin. This mechanism suggests a design for immunotoxins comprising a GUCY2C-directed monoclonal antibody conjugated through a reducible disulfide linkage to ricin A chain, which is activated to a potent cytotoxin in lysosomes. Indeed, this immunotoxin specifically killed GUCY2C-expressing colorectal cancer cells in a lysosomal- and clathrin-dependent fashion. Moreover, this immunotoxin reduced pulmonary tumors>80% (p<0.001), and improved survival 25% (p<0.001), in mice with established colorectal cancer metastases. Further, therapeutic efficacy was achieved without histologic evidence of toxicity in normal tissues. These observations support GUCY2C-targeted immunotoxins as novel therapeutics for metastatic tumors originating in the GI tract, including colorectum, stomach, esophagus, and pancreas.
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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.