Bottomly Daniel, Mathieson Chase, Vigoda Myles, Jeng Sophia, Evans Nathaniel, Anderson Ashley, Blucher Aurora, Lesch Aletha, Zheng Christina, Laderas Ted, Jacobs James, Kulesz-Martin Molly, McWeeney Shannon
OHSU Knight Cancer Institute, Portland, OR, 97239, USA.
OHSU School of Dentistry, Portland, OR, 97239, USA.
Sci Rep. 2025 Jun 5;15(1):19742. doi: 10.1038/s41598-025-03111-7.
Even though head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide, there are only two PD-1 targeted immunotherapies (pembrolizumab and nivolumab) and one tumor intrinsic EGFR targeted therapy (cetuximab) that are FDA approved for treatment of HNSCC. Taking advantage of a high throughput inhibitor assay and computational tools originally showing success in leukemia, we designed and employed HNSCC-specific inhibitor panels that capture the diversity of aberrational pathways in HNSCC to test viable cells derived from patients' HNSCC tumors. This provides a functional context to the multi-omic readouts conducted on these samples (mutations, protein expression and copy number alterations). In addition to generating these deeply characterized functional genomics datasets, we also developed additional visual analytics that have the potential to provide greater insight into HNSCC drug response patterns and potentially aid precision oncology tumor boards in evaluation and assessment of effective targeted therapeutic agents.
尽管头颈部鳞状细胞癌（HNSCC）是全球第七大常见癌症，但美国食品药品监督管理局（FDA）仅批准了两种针对程序性死亡受体1（PD-1）的免疫疗法（帕博利珠单抗和纳武利尤单抗）以及一种针对肿瘤内在表皮生长因子受体（EGFR）的疗法（西妥昔单抗）用于治疗HNSCC。利用最初在白血病治疗中取得成功的高通量抑制剂检测和计算工具，我们设计并采用了HNSCC特异性抑制剂组合，该组合涵盖了HNSCC中异常通路的多样性，用于测试源自患者HNSCC肿瘤的活细胞。这为对这些样本进行的多组学读数（突变、蛋白质表达和拷贝数改变）提供了功能背景。除了生成这些深度表征的功能基因组学数据集外，我们还开发了额外的视觉分析方法，这些方法有可能更深入地了解HNSCC的药物反应模式，并可能有助于精准肿瘤学肿瘤委员会评估和评价有效的靶向治疗药物。
