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.

项目总结