Targeting RNA helicase DDX3X with a small molecule inhibitor for breast cancer bone metastasis treatment.

Autor: Winnard PT Jr; Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA., Vesuna F; Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA., Bol GM; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA; Department of Medical Oncology, University Medical Center Utrecht Cancer Center, GA, Utrecht, the Netherlands., Gabrielson KL; Department of Molecular and Comparative Pathobiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Chenevix-Trench G; QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Locked Bag 2000, Brisbane, QLD, 4029, Australia., Ter Hoeve ND; Department of Pathology, University Medical Center Utrecht Cancer Center, 3508 GA, Utrecht, the Netherlands., van Diest PJ; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA; Department of Pathology, University Medical Center Utrecht Cancer Center, 3508 GA, Utrecht, the Netherlands., Raman V; Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA; Department of Pathology, University Medical Center Utrecht Cancer Center, 3508 GA, Utrecht, the Netherlands; Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. Electronic address: vraman2@jhmi.edu.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2024 Nov 01; Vol. 604, pp. 217260. Date of Electronic Publication: 2024 Sep 19.
DOI: 10.1016/j.canlet.2024.217260
Abstrakt: Patients who present with breast cancer bone metastasis only have limited palliative treatment strategies and efficacious drug treatments are needed. In breast cancer patient data, high levels of the RNA helicase DDX3 are associated with poor overall survival and bone metastasis. Consequently, our objective was to target DDX3 in a mouse breast cancer bone metastasis model using a small molecule inhibitor of DDX3, RK-33. Histologically confirmed live imaging indicated no bone metastases in the RK-33 treated cohort, as opposed to placebo-treated mice. We generated a cell line from a bone metastatic lesion in mouse and found that it along with a patient-derived bone metastasis cell line gained resistance to conventional chemotherapeutics but not to RK-33. Finally, differential levels of DDX3 were observed in breast cancer patient metastatic bone samples. Overall, this study indicates that DDX3 is a relevant clinical target in breast cancer bone metastasis and that RK-33 can be a safe and effective treatment for these patients.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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