靶向头颈癌HPV癌蛋白的基于protac的治疗方法

Nano TransMed Pub Date : 2025-12-01 Epub Date: 2025-01-16 DOI:10.1016/j.ntm.2025.100071
Nobendu Mukerjee , Dattatreya Mukherjee
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引用次数: 0

摘要

人类乳头状瘤病毒(HPV)相关头颈部癌症,特别是口咽鳞状细胞癌的发病率不断上升,突出表明需要在手术、放疗和化疗等传统模式之外的先进治疗选择,这些模式往往导致显著的发病率,并且缺乏针对该疾病分子发病机制的特异性。蛋白水解靶向嵌合体(PROTACs)提出了一种新的治疗策略,利用泛素-蛋白酶体系统特异性降解致癌的HPV蛋白E6和E7。这种有针对性的方法不仅潜在地减少了与传统治疗相关的副作用,而且还直接中断了这些蛋白质的促癌活性,为更有效、侵入性更小的hpv相关恶性肿瘤治疗提供了一条有希望的途径。
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PROTAC-based therapeutics for targeting HPV oncoproteins in head and neck cancers
The increasing incidence of Human Papillomavirus (HPV)-related head and neck cancers, particularly oropharyngeal squamous cell carcinomas, highlights the need for advanced therapeutic options beyond the traditional modalities of surgery, radiation, and chemotherapy, which often lead to significant morbidity and lack specificity in targeting the molecular pathogenesis of the disease. Proteolysis Targeting Chimeras (PROTACs) present a novel therapeutic strategy, leveraging the ubiquitin-proteasome system to specifically degrade the oncogenic HPV proteins E6 and E7. This targeted approach not only potentially reduces the side effects associated with conventional treatments but also directly interrupts the cancer-promoting activities of these proteins, offering a promising avenue for more effective and less invasive treatment of HPV-associated malignancies.
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