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

项目摘要 这种多样性补充的目标是为Maryum Cheema提供一个为期2年的培训途径，以扩大她 头颈部癌症的科学培训与保健差距研究。头颈部鳞状细胞 癌（HNSCC）是世界上第七常见的癌症，并且在口腔，口咽， 和喉。由于5年生存率为50%，因此迫切需要精确治疗的进步， HNSCC患者。基于人口的研究已经确定了HNSCC中种族群体之间的差异 治疗和生存，特别是对非洲血统的患者。即使在控制了 健康和获得保健的社会决定因素。HNSCC在黑人患者中的年轻发病率 与白色患者相比表明生物成分可能起作用。基因组和转录组 已经在癌症和个体癌症类型中评估了祖先的相关性。但大部分 这些研究在HNSCC的样本量上是有限的，根据自我报告定义种族， 考虑HPV状态或解剖亚型。正因为如此，一个可靶向突变或途径的子集 在非高加索人群中可能缺失。在基因组学研究的背景下， 因为在基于种族对患者进行定义和分层时必须使用基因组方法。 在这里，我们将填补这一空白领域的特点HNSCC肿瘤的分子特征，特别是在 通过计算（而不是自我报告）定义的非洲血统患者。这些分析将 给我们一个无偏估计的关系，血统/种族和HNSCC分子特征。除了DNA 此外，我们还将鉴定与HNSCC相关的转录组学变化。意志的路径分析 发现黑人患者的肿瘤脆弱性，这可能是治疗目标。 我们的初步分析确定了更高频率的MYC扩增和增加的MYC转录 在具有非洲血统的患者的HNSCC肿瘤中的活性，在本提案中，我们还将评估两个 新型MYC抑制剂作为HNSCC的靶向治疗。 总之，我们的工作将加深对非洲血统患者HNSCC的理解， 最终目标是开发个性化治疗和减少健康差距。

Project Summary The goal of this diversity supplement is to provide a 2-year training pathway for Maryum Cheema to expand her scientific training in head and neck cancer and health care disparity research. 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.