原癌基因 MYC 编码一种核转录因子，在多种细胞过程中发挥重要作用，例如细胞周期进展、增殖、代谢、粘附、凋亡和治疗耐药。 MYC 扩增在多种实体恶性肿瘤的侵袭性形式中持续观察到，并且与不良预后和远处转移相关。虽然 MYC 对头颈鳞状细胞癌 (HNSCC) 患者的致瘤作用众所周知，但该基因的扩增可能导致治疗耐药性的分子机制，尤其是对免疫检查点抑制剂的耐药性，仍待研究。在这里，我们介绍了一名复发/转移性 (R/M) HNSCC 患者的独特病例，尽管对基于纳武单抗的治疗最初有反应，但在获得 MYC 扩增后，该患者出现了快速进展的转移性疾病。我们在基线和进展时对该患者的肿瘤进行了比较转录组分析，以探究 MYC 可能赋予免疫治疗和/或放化疗耐药性的潜在分子过程，并使用 TCGA-HNSC 数据集和机构队列进一步探索临床病理特征和关键分子网络与 HNSCC 中 MYC 扩增相关。这项研究强调 MYC 扩增是免疫检查点抑制剂耐药的潜在机制，并建议将其用作 R/M HNSCC 的预测生物标志物和潜在治疗靶点。© 2024。作者。

The proto-oncogene MYC encodes a nuclear transcription factor that has an important role in a variety of cellular processes, such as cell cycle progression, proliferation, metabolism, adhesion, apoptosis, and therapeutic resistance. MYC amplification is consistently observed in aggressive forms of several solid malignancies and correlates with poor prognosis and distant metastases. While the tumorigenic effects of MYC in patients with head and neck squamous cell carcinoma (HNSCC) are well known, the molecular mechanisms by which the amplification of this gene may confer treatment resistance, especially to immune checkpoint inhibitors, remains under-investigated. Here we present a unique case of a patient with recurrent/metastatic (R/M) HNSCC who, despite initial response to nivolumab-based treatment, developed rapidly progressive metastatic disease after the acquisition of MYC amplification. We conducted comparative transcriptomic analysis of this patient's tumor at baseline and upon progression to interrogate potential molecular processes through which MYC may confer resistance to immunotherapy and/or chemoradiation and used TCGA-HNSC dataset and an institutional cohort to further explore clinicopathologic features and key molecular networks associated with MYC amplification in HNSCC. This study highlights MYC amplification as a potential mechanism of immune checkpoint inhibitor resistance and suggest its use as a predictive biomarker and potential therapeutic target in R/M HNSCC.© 2024. The Author(s).