Clinical study to evaluate the methylation signature of head and neck squamous cell carcinoma pain

评估头颈鳞状细胞癌疼痛甲基化特征的临床研究

基本信息

批准号：
10667307
负责人：
Chi T. Viet
金额：
$ 17.3万
依托单位：
LOMA LINDA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10667307
关键词：
Address Adenoviruses Advisory Committees Affect Anxiety Area Binding Bioinformatics Biological Markers Breast Brief Pain Inventory Cancer Control Cancer Pain Management Cancer Patient Clinical Clinical Research DNA Methylation Data Development Development Plans Disease Doctor of Philosophy Dose Eating Endothelin Endothelin B Receptor Enrollment Epigenetic Process European Organization for Research and Treatment of Cancer Exhibits Funding Gene Silencing Genes Goals Guidelines Head and Neck Cancer Head and Neck Squamous Cell Carcinoma High Prevalence Human Resources Hypermethylation Individual Intervention Knowledge Laboratories Lung Malignant Neoplasms Maps Mediating Mental Depression Mentorship Methylation Molecular Morphine Neoplasm Metastasis Neurons Opiate Addiction Opioid Pain Pain Measurement Pain management Pathway interactions Patients Persons Pharmaceutical Preparations Postdoctoral Fellow Pre-Clinical Model Prevalence Prospective Studies Prostate Quality of life Questionnaires Receptor Activation Research Research Project Grants Risk Role Scientist Series Structure Surgeon Time Tissues Training Translational Research Viral Genes Work alternative treatment antinociception cancer cell cancer pain cancer site cancer subtypes cancer therapy career career development clinical pain clinically relevant design drug discovery effective therapy endogenous opioids epigenetic silencing experience gene discovery gene product gene therapy genome wide methylation head and neck cancer patient improved inflammatory pain intense pain interest malignant mouth neoplasm meetings methylation pattern mouse model mu opioid receptors non-opioid analgesic novel opiate tolerance opioid epidemic pain model pain processing pain relief pre-clinical preclinical trial prescription opioid prospective psychosocial receptor expression research and development risk mitigation stress related disorder symptomatology therapeutic target translational research program translational study

项目摘要

ABSTRACT The proposed research and career development plan have been designed to facilitate my path toward becoming an independent surgeon scientist focused on highly translational head and neck squamous cell carcinoma (HNSCC) research. I have devoted my early research career to exploring epigenetic mechanisms (i.e., DNA methylation) of HNSCC pain, an area of research that has otherwise gone unnoticed. This proposal builds on my previous research in which I determine that hypermethylation of pain-mediating genes contribute to HNSCC pain in patients, and that hypomethylating agents treat HNSCC pain. The career development plan is carefully structured to hone my expertise in clinical research through a series of courses, national meetings, and meetings with my mentorship team. Upon completion of the K23, I will be well-prepared to apply for independent research funding through an R01 mechanism, which will support my translational research program focused on treatments for head and neck cancer pain. In this proposal I take a systematic approach to identify genes that are methylated in patients with severe HNSCC pain. In Aim 1 I prospectively enroll HNSCC patients, quantify their pain levels with validated pain questionnaires, and collect their cancer tissue for analysis with a genome-wide methylation array. I will analyze the methylation data and identify a suite of hypermethylated genes in patients with severe pain. I have proven feasibility of this approach through preliminary studies, in which I used existing methylation data in HNSCC patients to identify a list of hypermethylated genes. Many of these genes have not previously been associated with pain processing. In Aim 2, I focus on one hypermethylated gene and determine whether adenovirus therapy to re-express the gene produces antinociception in the preclinical model. The project is impactful because it explores a pain mechanism that is largely unknown. The results will establish the methylation signature of HNSCC pain. These genes could be targeted with either gene therapy or hypomethylating agents to treat HNSCC pain, offering non-opioid alternatives and making the research clinically relevant, especially with the current opioid crisis. My mentorship and advisory team is comprised of individuals who have expert knowledge in all aspects of translational and clinical research, specifically in the areas of cancer, pain, bioinformatics, and drug discovery, all of which are critical for the proposed research. I receive protected time, laboratory space, start-up funding, and personnel support. The career development plan and proposed research will bring me closer to realizing my career goal of developing highly effective treatments for head and neck cancer pain.

抽象的拟议的研究和职业发展计划旨在促进我的道路成为一名独立的外科医生科学家，专注于高度转化的头颈鳞状细胞癌症（HNSCC）研究。我早期的研究生涯致力于探索表观遗传机制 HNSCC 疼痛（即 DNA 甲基化），这是一个一直被忽视的研究领域。这个提议基于我之前的研究，我确定疼痛介导基因的过度甲基化有助于患者的 HNSCC 疼痛，以及低甲基化药物可治疗 HNSCC 疼痛。职业发展计划经过精心设计，通过一系列课程、全国会议来磨练我在临床研究方面的专业知识，以及与我的导师团队的会议。完成 K23 后，我将为申请做好充分准备通过 R01 机制提供独立研究经费，这将支持我的转化研究计划专注于头颈癌疼痛的治疗。在本提案中，我采用系统方法来识别重症患者中甲基化的基因头颈部鳞癌疼痛。在目标 1 中，我前瞻性地招募 HNSCC 患者，通过经过验证的疼痛来量化他们的疼痛水平调查问卷，并收集他们的癌症组织，用全基因组甲基化阵列进行分析。我来分析一下甲基化数据并识别出剧烈疼痛患者的一组高甲基化基因。我已经证明了通过初步研究证明了这种方法的可行性，其中我使用了 HNSCC 中现有的甲基化数据患者识别高甲基化基因列表。其中许多基因以前从未关联过与疼痛处理。在目标 2 中，我关注一个高甲基化基因并确定腺病毒治疗是否可行在临床前模型中重新表达该基因会产生抗伤害作用。该项目具有影响力，因为它探索一种很大程度上未知的疼痛机制。结果将建立甲基化特征头颈部鳞癌疼痛。这些基因可以通过基因疗法或低甲基化药物来治疗 HNSCC 疼痛，提供非阿片类药物替代品并使研究具有临床相关性，特别是与当前的阿片类药物危机。我的指导和咨询团队由在各个方面都拥有专业知识的个人组成转化和临床研究，特别是在癌症、疼痛、生物信息学和药物发现领域，所有这些对于拟议的研究都至关重要。我获得受保护的时间、实验室空间、启动资金，和人员支持。职业发展计划和拟议的研究将使我更接近实现我的目标开发针对头颈癌疼痛的高效治疗方法的职业目标。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Brush swab as a noninvasive surrogate for tissue biopsies in epigenomic profiling of oral cancer.

刷拭子作为口腔癌表观基因组分析中组织活检的无创替代品。

DOI：
发表时间：
2021-12-20
期刊：
影响因子：
11.1
作者：
Viet, Chi T;Zhang, Xinyu;Xu, Ke;Yu, Gary;Asam, Kesava;Thomas, Carissa M;Callahan, Nicholas F;Doan, Coleen;Walker, Paul C;Nguyen, Khanh;Kidd, Stephanie C;Lee, Steve C;Grandhi, Anupama;Allen, Clint T;Young, Simon;Melville, James C;Shum, Jona
通讯作者：
Shum, Jona

Advances in Head and Neck Cancer Pain.

头颈癌疼痛的进展。

DOI：
发表时间：
2022-08
期刊：
影响因子：
7.6
作者：
Ye, Y;Jensen, D D;Viet, C T;Pan, H L;Campana, W M;Amit, M;Boada, M D
通讯作者：
Boada, M D

Repurposing EGFR Inhibitors for Oral Cancer Pain and Opioid Tolerance.

重新利用 EGFR 抑制剂治疗口腔癌疼痛和阿片类药物耐受性。

DOI：
发表时间：
2023-11-03
期刊：
影响因子：
0
作者：
Santi, Maria Daniela;Zhang, Morgan;Liu, Naijiang;Viet, Chi T;Xie, Tongxin;Jensen, Dane D;Amit, Moran;Pan, Huilin;Ye, Yi
通讯作者：
Ye, Yi

Advances in Tissue Engineering and Implications for Oral and Maxillofacial Reconstruction.

组织工程的进展及其对口腔颌面重建的影响。

DOI：
发表时间：
2021-11
期刊：
影响因子：
0
作者：
McGue, Caitlyn M;Mañón, Victoria A;Viet, Chi T
通讯作者：
Viet, Chi T

Schwann Cells Induce Phenotypic Changes in Oral Cancer Cells.

雪旺细胞诱导口腔癌细胞表型变化。

DOI：
发表时间：
2022-09
期刊：
影响因子：
3.7
作者：
Santi, Maria Daniela;Zhang, Morgan;Salvo, Elizabeth;Asam, Kesava;Viet, Chi T;Xie, Tongxin;Amit, Moran;Aouizerat, Bradley;Ye, Yi
通讯作者：
Ye, Yi