AI Article Synopsis
- Patients with breast cancer that has spread to bones face limited treatment options, and high levels of RNA helicase DDX3 are linked to worse survival.
- In a study using a mouse model, treatment with the DDX3 inhibitor RK-33 resulted in no bone metastases, unlike the placebo group.
- The research suggests that DDX3 is an important target for treatment in breast cancer bone metastasis, with RK-33 showing potential as a safe and effective option.
Article Abstract
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.
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| http://dx.doi.org/10.1016/j.canlet.2024.217260 | DOI Listing |
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