文章：

Indisulam对HPV阳性和HPV阴性头颈癌均显示出抗癌效果

Indisulam Shows an Anti-Cancer Effect on HPV+ and HPV− Head and Neck Cancer

原文发布日期：22 March 2025

DOI: 10.3390/cancers17071072

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: HPV+ head and neck squamous cell carcinoma has been shown to have a unique genomic background, requiring researchers to study it as its own distinct type of cancer. HPV+ tumors have been shown to exhibit fewer genetic mutations in cancer drivers as opposed to their HPV− counterparts. In this paper, we explored how targeting post-transcriptional changes, specifically alternative splicing events, could serve as a potential mechanism to treat HPV+ cancer.Methods: Using indisulam, a drug that targets alternative splicing through the degradation of RBM39, we treated various HPV+ and HPV− cell lines and assessed tumor cell viability. We also tested indisulam in vivo to evaluate its effect on tumor volume. Additionally, we analyzed gene expression differences between indisulam-treated subjects and their non-treated counterparts.Results: Indisulam treatment led to a reduction in tumor cell viability in both HPV+ and HPV− cell lines. In vivo experiments showed a reduction in tumor volume following indisulam treatment. Gene expression analysis revealed that indisulam induces consistent differential gene expression changes and highly enriches interferon pathways in treated HPV+ cell lines.Conclusions: These findings suggest that targeting alternative splicing via indisulam may be a promising therapeutic approach for HPV+ cancers. Further research is required to establish indisulam as a viable anti-cancer treatment in clinical settings.

摘要翻译： 

背景/目的：人乳头瘤病毒阳性（HPV+）头颈部鳞状细胞癌已被证实具有独特的基因组背景，这要求研究者将其作为一种独立的癌症类型进行研究。与HPV阴性（HPV−）肿瘤相比，HPV+肿瘤在癌症驱动基因中表现出更少的基因突变。本文探讨了靶向转录后变化，特别是选择性剪接事件，作为治疗HPV+癌症的潜在机制。 方法：使用通过降解RBM39靶向选择性剪接的药物indisulam，我们处理了多种HPV+和HPV−细胞系，并评估了肿瘤细胞的存活率。同时，我们在体内实验中测试了indisulam，以评估其对肿瘤体积的影响。此外，我们分析了经indisulam处理的样本与未处理样本之间的基因表达差异。 结果：Indisulam处理导致HPV+和HPV−细胞系中肿瘤细胞存活率均有所下降。体内实验显示，indisulam治疗后肿瘤体积减小。基因表达分析表明，indisulam在处理的HPV+细胞系中诱导了一致的差异基因表达变化，并高度富集了干扰素通路。 结论：这些发现表明，通过indisulam靶向选择性剪接可能是治疗HPV+癌症的一种有前景的治疗方法。需要进一步研究以确立indisulam在临床环境中作为一种可行的抗癌治疗手段。

原文链接：

Indisulam Shows an Anti-Cancer Effect on HPV+ and HPV− Head and Neck Cancer