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

鉴定非洲血统患者头颈癌的分子亚型

• 批准号: 10452965
• 负责人: Fatemeh Momen Heravi
• 金额: $ 9.92万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-03 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10452965
• 关键词: African; Anatomy; Biological; DNA Sequence Alteration; Development; Frequencies; Genetic Transcription; Genomics; Goals; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Health Services Accessibility; Human Papillomavirus; Incidence; Individual; Larynx; Malignant Neoplasms; Methods; Molecular; Molecular Profiling; Mutation; Oral cavity; Oropharyngeal; Outcome; Pathway Analysis; Pathway interactions; Patient Self-Report; Patients; Population; Population Study; Precision therapeutics; Protocols documentation; Race; Research; Sample Size; Survival Rate; Testing; Training; Treatment outcome; Work; base; black patient; cancer care; cancer type; genomic profiles; health care disparity; health disparity; improved; inhibitor/antagonist; molecular subtypes; novel; patient population; patient stratification; personalized medicine; profiles in patients; social health determinants; targeted treatment; therapeutic target; tool; transcriptomics; tumor

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.

项目摘要 这个多样性补充的目标是为Maryum Cheema提供为期2年的培训途径，以扩大Her 头颈部癌症和医疗保健差距研究方面的科学培训。头颈部鳞状细胞 癌症(HNSCC)是世界上第七大常见癌症，见于口腔、口咽、 还有喉咙。随着五年存活率达到50%，精准治疗的进步是迫切需要的 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，特别是非洲血统的患者。即使在控制后，这种差距仍然存在 健康和获得护理的社会决定因素。黑人患者中HNSCC的年轻发病率 与白人患者相比，这表明可能是生物因素造成的。基因组和转录组 对不同癌症和不同癌症类型的血统相关性进行了评估。然而，大多数 这些研究限制了HNSCC的样本量，定义了基于自我报告的种族，并且没有 被认为是HPV状态或解剖亚型。正因为如此，靶向突变或通路的子集 可能在非高加索人群中缺失。在基因组学研究的背景下，更准确的工具 因为在根据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。 我们的初步分析确定了MYC扩增的频率更高，MYC转录增加 非洲血统患者的HNSCC肿瘤中的活性。在这项建议中，我们还将评估两种 作为HNSCC靶向治疗的新型MYC抑制剂。 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。