The emerging landscape for next-generation HNSCC treatment.

IF 24 1区医学 Q1 PHARMACOLOGY & PHARMACY

Trends in pharmacological sciences Pub Date : 2026-09-22 DOI:10.1016/j.tips.2026.09.007

Kailey N Jackett, Meghri Katerji, Kiranya Arnold, Kyunghee Burkitt, Andrew Gennaro, Vassiliki Saloura, John Brognard

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引用次数: 0

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a biologically complex malignancy in which durable responses to standard multimodal therapies, targeted therapies, and immune checkpoint inhibitors remain limited. Therapeutic resistance arises from interconnected oncogenic signaling, tumor plasticity, heterogeneity, and immune evasion, which enable tumors to bypass inhibition of individual pathways. These mechanisms also differ across biologically distinct HNSCC subsets, including human papillomavirus (HPV)-positive and HPV-negative disease. Emerging therapeutic platforms in preclinical and clinical development, including targeted protein degraders, engineered antibodies, cellular and vaccine-based immunotherapies, photoimmunotherapy, and epigenetic modulators, provide new opportunities to target these interconnected vulnerabilities. In this review, we examine how these pharmacological strategies may overcome resistance in HNSCC and discuss their integration into biomarker-guided, mechanism-driven combination regimens.

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下一代HNSCC治疗的新兴前景。

头颈部鳞状细胞癌（HNSCC）是一种生物学复杂的恶性肿瘤，对标准多模式治疗、靶向治疗和免疫检查点抑制剂的持久反应仍然有限。治疗耐药源于相互关联的致癌信号、肿瘤可塑性、异质性和免疫逃避，这些因素使肿瘤能够绕过单个途径的抑制。这些机制在生物学上不同的HNSCC亚群中也有所不同，包括人乳头瘤病毒（HPV）阳性和HPV阴性疾病。临床前和临床开发中的新兴治疗平台，包括靶向蛋白质降解剂、工程化抗体、细胞和基于疫苗的免疫疗法、光免疫疗法和表观遗传调节剂，为靶向这些相互关联的脆弱性提供了新的机会。在这篇综述中，我们研究了这些药物策略如何克服HNSCC的耐药性，并讨论了它们与生物标志物引导、机制驱动的联合方案的整合。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Trends in pharmacological sciences 医学-药学

CiteScore

23.90

自引率

0.70%

发文量

132

审稿时长

6-12 weeks

期刊介绍： Trends in Pharmacological Sciences (TIPS) is a monthly peer-reviewed reviews journal that focuses on a wide range of topics in pharmacology, pharmacy, pharmaceutics, and toxicology. Launched in 1979, TIPS publishes concise articles discussing the latest advancements in pharmacology and therapeutics research. The journal encourages submissions that align with its core themes while also being open to articles on the biopharma regulatory landscape, science policy and regulation, and bioethics. Each issue of TIPS provides a platform for experts to share their insights and perspectives on the most exciting developments in the field. Through rigorous peer review, the journal ensures the quality and reliability of published articles. Authors are invited to contribute articles that contribute to the understanding of pharmacology and its applications in various domains. Whether it's exploring innovative drug therapies or discussing the ethical considerations of pharmaceutical research, TIPS provides a valuable resource for researchers, practitioners, and policymakers in the pharmacological sciences.