ArticleEuropean journal of nuclear medicine and molecular imaging2016
Molecular imaging of EGFR and CD44v6 for prediction and response monitoring of HSP90 inhibition in an in vivo squamous cell carcinoma model.
Article in European journal of nuclear medicine and molecular imaging, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 28 citations in OpenAlex.
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- Radiotheranostic Targeting Cancer Stem Cells in Human Colorectal Cancer Xenografts.Molecular imaging and biology · 2020Article
- Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks.Nanomaterials (Basel, Switzerland) · 2020Article
- Enhancing the therapeutic effects of in vitro targeted radionuclide therapy of 3D multicellular tumor spheroids using the novel stapled MDM2/X-p53 antagonist PM2.EJNMMI research · 2020Article
- The HSP90 inhibitor Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy: an in vitro and in vivo approach.Scientific reports · 2020Article
- The radiosensitizer Onalespib increases complete remission inEuropean journal of nuclear medicine and molecular imaging · 2020Article
- The HSP90 inhibitor onalespib potentiates 177Lu‑DOTATATE therapy in neuroendocrine tumor cells.International journal of oncology · 2019Article
- Real-time molecular optical micro-imaging of EGFR mutations using a fluorescent erlotinib based tracer.BMC pulmonary medicine · 2019Article
- Evaluation of [Theranostics · 2019Article
- Radiolabeled F(ab')Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Article
- The Promise of Novel Biomarkers for Head and Neck Cancer from an Imaging Perspective.International journal of molecular sciences · 2018Review
- Preclinical evaluation of a novel engineered recombinant human anti-CD44v6 antibody for potential use in radio-immunotherapy.International journal of oncology · 2018Article
- Molecularly targeted therapies in cancer: a guide for the nuclear medicine physician.European journal of nuclear medicine and molecular imaging · 2017Review
- CD44v6-Targeted Imaging of Head and Neck Squamous Cell Carcinoma: Antibody-Based Approaches.Contrast media & molecular imaging · 2017Review
- MicroPET/CT Imaging of AXL Downregulation by HSP90 Inhibition in Triple-Negative Breast Cancer.Contrast media & molecular imaging · 2017Article
- A High-Affinity Repebody for Molecular Imaging of EGFR-Expressing Malignant Tumors.Theranostics · 2017Article
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6 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
purposeHeat shock protein 90 (HSP90) is essential for the activation and stabilization of numerous oncogenic client proteins. AT13387 is a novel HSP90 inhibitor promoting degradation of oncogenic proteins upon binding, and may also act as a radiosensitizer. For optimal treatment there is, however, the need for identification of biomarkers for patient stratification and therapeutic response monitoring, and to find suitable targets for combination treatments. The aim of this study was to assess the response of surface antigens commonly expressed in squamous cell carcinoma to AT13387 treatment, and to find suitable biomarkers for molecular imaging and radioimmunotherapy in combination with HSP90 inhibition.
methodsCancer cell proliferation and radioimmunoassays were used to evaluate the effect of AT13387 on target antigen expression in vitro. Inhibitor effects were then assessed in vivo in mice-xenografts. Animals were treated with AT13387 (5 × 50 mg/kg), and were imaged with PET using either (18)F-FDG or (124)I-labelled tracers for EGFR and CD44v6, and this was followed by ex-vivo biodistribution analysis and immunohistochemical staining.
resultsAT13387 exposure resulted in high cytotoxicity and possible radiosensitization with IC50 values below 4 nM. Both in vitro and in vivo AT13387 effectively downregulated HSP90 client proteins. PET imaging with (124)I-cetuximab showed a significant decrease of EGFR in AT13387-treated animals compared with untreated animals. In contrast, the squamous cell carcinoma-associated biomarker CD44v6, visualized with (124)I-AbD19384 as well as (18)F-FDG uptake, were not significantly altered by AT13387 treatment.
conclusionWe conclude that AT13387 downregulates HSP90 client proteins, and that molecular imaging of these proteins may be a suitable approach for assessing treatment response. Furthermore, radioimmunotherapy targeting CD44v6 in combination with AT13387 may potentiate the radioimmunotherapy outcome due to radiosensitizing effects of the drug, and could potentially lead to a lower dose to normal tissues.
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