Identifying Molecular Subtypes of Head and Neck Cancer in Patients with African Ancestry

项目摘要 头颈部鳞状细胞癌(HNSCC)是世界上第7大最常见的癌症。 在口腔、口咽和喉部。随着五年存活率达到50%，精确治疗取得了进展 是HNSCC患者迫切需要的。基于人口的研究发现了不同种族之间的差异 HNSCC群体的治疗和生存，特别是非洲血统的患者。这种差距甚至存在 在控制了健康和获得护理的社会决定因素之后。黑人中HNSCC的年轻发病率 患者与白人患者的比较表明，生物成分可能起到了作用。基因组和 对不同癌症类型和不同癌症类型的祖先的转录相关进行了评估。 然而，大多数这些研究都限制了HNSCC的样本量，定义了基于自我报告的种族，以及 没有考虑HPV状态或解剖亚型。正因为如此，靶向突变的子集或 对于非高加索人群来说，这条途径可能会缺失。在基因组学研究的背景下，更准确 在根据种族对患者进行定义和分层时，必须使用诸如基因组方法之类的工具。 在这里，我们将通过具体描述HNSCC肿瘤的分子特征来填补这一领域的空白 非洲血统的患者，根据计算(而不是通过自我报告)定义。这些分析将 给我们一个对血统/种族和HNSCC分子特征的关系的公正的估计。除了DNA 此外，我们还将确定与HNSCC相关的转录改变。意志的路径分析 发现黑人患者的肿瘤脆弱性，这可能是治疗的目标。我们的初步分析 在HNSCC肿瘤中发现更高频率的MYC扩增和MYC转录活性增加 有非洲血统的患者。在这项提案中，我们还将评估两种新型MYC抑制剂作为一种 HNSCC的靶向治疗。 综上所述，我们的工作将加深对非洲血统患者HNSCC的了解， 开发个性化治疗和减少健康差距的最终目标。

Project Summary Head and neck squamous cell carcinoma (HNSCC) is the 7th most common cancer worldwide and is observed in the oral cavity, oropharynx, and larynx. With a 5-year survival rate of fifty percent, precision therapy advances are desperately needed for HNSCC patients. Population-based studies have identified disparities between racial groups in HNSCC treatment and survival, especially for patients with African ancestry. This disparity exists even after controlling for social determinants of health and access to care. The younger incidence of HNSCC in black patients compared to white patients suggests a biological component may be contributing. Genomic and transcriptomic correlations for ancestry have been assessed across cancer and in individual cancer types. However, most of these studies are limited in sample size for HNSCCs, define race based on self-reporting, and have not considered HPV status or anatomical subtype. Because of this, a subset of targetable mutations or pathways could be missing for non-caucasian populations. In the context of genomics research, more accurate tools such as genomic methods must be used when defining and stratifying patients based on race. Here, we will fill this gap in the field by characterizing the molecular features of HNSCC tumors specifically in patients with African ancestry, as defined computationally (rather than by self-reporting). These analyses will give us an unbiased estimate of the relation of ancestry/race and HNSCC molecular features. In addition to DNA alterations, we will also identify transcriptomic changes associated with HNSCC. Pathway analysis of will uncover tumor vulnerabilities in black patients which may be therapeutic targets. Our preliminary analysis identified a higher frequency of MYC amplifications and increased MYC transcriptional activity in HNSCC tumors of patients with African ancestry. In this proposal, we will also assess the utility of two novel MYC inhibitors as a targeted therapy for HNSCC. Taken together, our work will deepen the understanding of HNSCC in patients with African ancestry, with the ultimate goal of developing personalized therapies and reducing health disparities.