AI Article Synopsis
- * Researchers explored the use of small interfering RNAs (siRNAs) targeting the BRD4-NUTM1 fusion (B4N), the most prevalent type in NC, to assess their potential as a treatment option and evaluated patient blood samples for treatment response.
- * The study found that B4N-specific siRNA effectively inhibited the fusion transcript and protein, reducing cell growth and tumor size, while levels of the fusion transcript in patient samples correlated with treatment responsiveness, indicating a pathway for precision medicine in managing NC.
Article Abstract
Purpose: NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC.
Materials And Methods: We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts.
Results: As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness.
Conclusion: This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10101799 | PMC |
| http://dx.doi.org/10.4143/crt.2022.910 | DOI Listing |
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