ArticleOncotarget2015
DNA damage induces GDNF secretion in the tumor microenvironment with paracrine effects promoting prostate cancer treatment resistance.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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
35 citing papers in PubMed, 54 citations in OpenAlex.
- Neural regulation of tumor immunity: emerging opportunities to enhance cancer immunotherapy.Experimental & molecular medicine · 2026Review
- Circulatory prostate cancer proteome landscapes and prognostic biomarkers in metastatic castrate resistant prostate cancer.Clinical proteomics · 2025Article
- The contribution of the nervous system in the cancer progression.BMB reports · 2024Review
- Chemotherapy-initiated cysteine-rich protein 61 decreases acute B-lymphoblastic leukemia chemosensitivity.Journal of cancer research and clinical oncology · 2024Article
- A network map of GDNF/RET signaling pathway in physiological and pathological conditions.Journal of cell communication and signaling · 2023Article
- Nanomedicine Strategies for Targeting Tumor Stroma.Cancers · 2023Review
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- Downregulation of miR-211-5p Promotes Carboplatin Resistance in Human Retinoblastoma Y79 Cells by Affecting the GDNF-LIF Interaction.Frontiers in oncology · 2022Article
- RET signaling pathway and RET inhibitors in human cancer.Frontiers in oncology · 2022Review
- Serum Glial Cell Line-Derived Neurotrophic Factor (sGDNF) Is a Novel Biomarker in Predicting Cirrhosis in Patients with Chronic Hepatitis B.Canadian journal of gastroenterology & hepatology · 2022Article
- The Emerging Portrait of Glial Cell Line-derived Neurotrophic Factor Family Receptor Alpha (GFRα) in Cancers.International journal of medical sciences · 2022Review
- Development of a model for fibroblast-led collective migration from breast cancer cell spheroids to study radiation effects on invasiveness.Radiation oncology (London, England) · 2021Article
- Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer.Scientific reports · 2021Article
- Investigation of Neural Microenvironment in Prostate Cancer in Context of Neural Density, Perineural Invasion, and Neuroendocrine Profile of Tumors.Frontiers in oncology · 2021Article
- New Insights into Therapy-Induced Progression of Cancer.International journal of molecular sciences · 2020Review
- Supraphysiological androgens suppress prostate cancer growth through androgen receptor-mediated DNA damage.The Journal of clinical investigation · 2019Article
- Tumor microenvironment-driven non-cell-autonomous resistance to antineoplastic treatment.Molecular cancer · 2019Review
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Though metastatic cancers often initially respond to genotoxic therapeutics, acquired resistance is common. In addition to cytotoxic effects on tumor cells, DNA damaging agents such as ionizing radiation and chemotherapy induce injury in benign cells of the tumor microenvironment resulting in the production of paracrine-acting factors capable of promoting tumor resistance phenotypes. In studies designed to characterize the responses of prostate and bone stromal cells to genotoxic stress, we found that transcripts encoding glial cell line-derived neurotrophic factor (GDNF) increased several fold following exposures to cytotoxic agents including radiation, the topoisomerase inhibitor mitoxantrone and the microtubule poison docetaxel. Fibroblast GDNF exerted paracrine effects toward prostate cancer cells resulting in enhanced tumor cell proliferation and invasion, and these effects were concordant with the expression of known GDNF receptors GFRA1 and RET. Exposure to GDNF also induced tumor cell resistance to mitoxantrone and docetaxel chemotherapy. Together, these findings support an important role for tumor microenvironment damage responses in modulating treatment resistance and identify the GDNF signaling pathway as a potential target for improving responses to conventional genotoxic therapeutics.
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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.