ArticleJCI insight2021
SPINK1 as a plasma marker for tumor hypoxia and a therapeutic target for radiosensitization.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Inhibition of autotaxin sensitizes colon cancer to radiation by suppressing LPAR2-AKT survival signaling.BMC gastroenterology · 2025Article
- Dual tissue mRNA and serum protein signatures improve risk stratification in hepatocellular carcinoma.NPJ precision oncology · 2025Article
- Exploratory Study of Prognostic Plasma Biomarkers in Patients with Pulmonary Arterial Hypertension.The American journal of pathology · 2025Article
- UPR-induced intracellular C5aR1 promotes adaptation to the hypoxic tumour microenvironment.Cell death & disease · 2025Article
- Revolutionizing cancer therapy: Monoclonal antibodies in radiosensitization.BioImpacts : BI · 2025Review
- An integrative proteomics approach identifies tyrosine kinase KIT as a therapeutic target for SPINK1-positive prostate cancer.iScience · 2024Article
- Article
- Myriad factors and pathways influencing tumor radiotherapy resistance.Open life sciences · 2024Review
- A positive feedback loop between ID3 and PPARγ via DNA damage repair regulates the efficacy of radiotherapy for rectal cancer.BMC cancer · 2023Article
- Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Prognostic Factors for the Efficiency of Radiation Therapy in Dogs with Oral Melanoma: A Pilot Study of Hypoxia in Intraosseous Lesions.Veterinary sciences · 2022Article
- Cuproptosis identifies respiratory subtype of renal cancer that confers favorable prognosis.Apoptosis : an international journal on programmed cell death · 2022Article
- Lung transcriptome of nonhuman primates exposed to total- and partial-body irradiation.Molecular therapy. Nucleic acids · 2022Article
- SPINKs in Tumors: Potential Therapeutic Targets.Frontiers in oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Hypoxia is associated with tumor radioresistance; therefore, a predictive marker for tumor hypoxia and a rational target to overcome it have been sought to realize personalized radiotherapy. Here, we show that serine protease inhibitor Kazal type I (SPINK1) meets these 2 criteria. SPINK1 expression was induced upon hypoxia (O2 < 0.1%) at the transcription initiation level in a HIF-dependent manner, causing an increase in secreted SPINK1 levels. SPINK1 proteins were detected both within and around hypoxic regions of xenografted and clinical tumor tissues, and their plasma levels increased in response to decreased oxygen supply to xenografts. Secreted SPINK1 proteins enhanced radioresistance of cancer cells even under normoxic conditions in EGFR-dependent and nuclear factor erythroid 2-related factor 2-dependent (Nrf2-dependent) manners and accelerated tumor growth after radiotherapy. An anti-SPINK1 neutralizing antibody exhibited a radiosensitizing effect. These results suggest that SPINK1 secreted from hypoxic cells protects the surrounding and relatively oxygenated cancer cells from radiation in a paracrine manner, justifying the use of SPINK1 as a target for radiosensitization and a plasma marker for predicting tumor hypoxia.
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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.