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: 10445340
• 负责人: Fatemeh Momen Heravi
• 金额: $ 16.2万
• 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: 2021-07-07 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10445340
• 关键词: Affect; African ancestry; Age; Anatomy; Biological; Characteristics; Clinical; DNA Sequence Alteration; Data; Data Set; Development; Disease Progression; Frequencies; Genes; Genetic; Genetic Transcription; Genomics; Goals; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Health Services Accessibility; Human Papillomavirus; Incidence; Individual; Knowledge; Larynx; Lead; Malignant Neoplasms; Methods; Modality; Molecular; Molecular Profiling; Molecular Target; Mutate; Mutation; Neoplasm Metastasis; Nose; Operative Surgical Procedures; Oral cavity; Oropharyngeal; Outcome; Pathway Analysis; Pathway interactions; Patient Self-Report; Patients; Pattern; Pharyngeal structure; Population; Population Study; Precision therapeutics; Prognosis; Protocols documentation; Race; Recurrence; Reduce health disparities; Regulator Genes; Research; Risk; Risk Assessment; Risk Factors; Role; Sample Size; Sampling; Socioeconomic Status; Survival Rate; Testing; The Cancer Genome Atlas; Therapeutic; Treatment outcome; Universities; Work; base; black patient; cancer type; clinical prognosis; cohort; genome sequencing; genomic profiles; health disparity; improved; inhibitor; large datasets; minority patient; molecular subtypes; molecular targeted therapies; novel; patient population; patient stratification; personalized management; personalized medicine; precision medicine; profiles in patients; screening; social health determinants; survival outcome; targeted treatment; therapeutic target; tool; transcriptome sequencing; transcriptomics; treatment planning; tumor; tumorigenesis; whole genome

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.

项目概要 头颈鳞状细胞癌 (HNSCC) 是全球第七大最常见癌症，据观察 在口腔、口咽和喉中。精准治疗取得进展，五年生存率为百分之五十 HNSCC 患者迫切需要。基于人口的研究已经确定了种族之间的差异 组的 HNSCC 治疗和生存率，特别是对于非洲血统的患者。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。黑人头颈部鳞癌发病率较年轻 与白人患者相比，这表明生物因素可能起作用。基因组和 祖先的转录组相关性已经在癌症和个体癌症类型中进行了评估。 然而，大多数这些研究的 HNSCC 样本量有限，基于自我报告来定义种族，并且 没有考虑 HPV 状态或解剖亚型。因此，可靶向突变的子集或 非白人群体可能会缺失途径。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，必须使用基因组方法等工具。 在这里，我们将通过表征 HNSCC 肿瘤的分子特征来填补该领域的空白，特别是 具有非洲血统的患者，根据计算定义（而不是通过自我报告）。这些分析将 让我们对血统/种族和 HNSCC 分子特征之间的关系进行公正的估计。除了DNA 改变，我们还将鉴定与 HNSCC 相关的转录组变化。意志路径分析 揭示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 在 HNSCC 肿瘤中发现了更高频率的 MYC 扩增和增加的 MYC 转录活性 具有非洲血统的患者。在本提案中，我们还将评估两种新型 MYC 抑制剂作为药物的效用。 HNSCC 的靶向治疗。 总而言之，我们的工作将加深对非洲血统患者 HNSCC 的了解， 开发个性化疗法和减少健康差异的最终目标。