Cancer Prevention-Interception Against MGUS Progression

癌症预防——阻止 MGUS 进展

基本信息

批准号：
10745010
负责人：
Yong Li
金额：
$ 116.61万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10745010
关键词：
Affect Age Years American Amyloid Automobile Driving Blood Bone Marrow Bone Marrow Cells Cancer Center Chemicals Chemoprevention Chronic Lymphocytic Leukemia Communication Consensus DNA Vaccines Dedications Development Diagnosis Diagnostic Disease Funding Ganciclovir Goals Hematological Disease IgE Immunoglobulin A Immunoglobulin D Immunoglobulin G Immunoglobulin M Immunoglobulins Immunologics Immunoprevention In Vitro Infrastructure Intercept Intervention Investigation Life Expectancy Light Light-Chain Immunoglobulins Lymphoid Malignant Neoplasms Molecular Monoclonal gammopathy of uncertain significance Multiple Myeloma Mutate Network Infrastructure Non-Hodgkin&apos s Lymphoma Oncogenic Oncoproteins Patients Persons Plasmacytoma Population Population Control Precancerous Conditions Prevention Preventive Process Protein Secretion Proteins Recommendation Research Research Personnel Research Project Grants Risk Risk Factors Role Specialized Center Syndrome Testing Waldenstrom Macroglobulinemia cancer diagnosis cancer invasiveness cancer prevention cancer risk clinical practice early phase clinical trial efficacy evaluation follow-up high risk in vivo innovation multiple myeloma M Protein novel precision cancer prevention precision oncology prevent primary amyloidosis of light chain type programs progression risk research and development senescence small molecule targeted agent tumor initiation tumor progression ubiquitin-protein ligase

项目摘要

Project Summary Monoclonal gammopathy of undetermined significance (MGUS) is a precancerous condition in which a person has moderately elevated levels of an abnormal immunoglobulin (Ig) protein (called M protein) in the blood. MGUS patients have a cancer risk ~6.5 times as high as the control population. MGUS may progress to multiple myeloma (MM), Waldenström macroglobulinemia (WM), non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), amyloid light-chain (AL) amyloidosis, or plasmacytoma. MM, WM, a large portion of NHL, and AL amyloidosis are incurable diseases. CLL and plasmacytoma are rarely cured. The significance of MGUS calls for a cancer prevention-interception U54 Specialized Center dedicated to this precancerous condition  MGUS affects ~1% of the population, MGUS progresses to cancer or other associated blood disorders persistently at a rate of ~1% per year, and ~90% cancer/disorder that progressed from MGUS are incurable. All patients with MGUS are potential candidates for cancer prevention and interception. We hypothesize that cancer-driving molecules and the bone marrow microenvironment promoting MGUS progression are suitable targets for precision cancer prevention and interception. We propose to establish the Cancer Prevention-Interception against MGUS Progression to Cancer (CAP-MGUS) Center as an agile and effective network infrastructure dedicated to preventing MGUS progression. This Center will undertake collaborative research focusing on immunologically and chemically targeted agents that prevent or intercept the oncogenic process in patients with MGUS or smoldering diseases. We propose three aims to achieve the CAP-MGUS Center’s overarching goal. In Aim 1, we will functionally validate several oncotargets in tumor initiation and progression to invasive cancer and ascertain their suitability for targeted intervention strategies. In Aim 2, we will discover innovative immuno- and chemo-prevention and interception agents through in vitro and in vivo efficacy evaluation. In Aim 3, we will develop new projects by identifying novel targets for cancer- preventive or interceptive interventions against MGUS progression. Collectively, we expect to obtain chemoprevention and immunoprevention agents for further development or earlier phase clinical trials.

项目概要意义未明的单克隆伽马病 (MGUS) 是一种癌前病变，患者患有这种病血液中异常免疫球蛋白 (Ig) 蛋白（称为 M 蛋白）水平中度升高。 MGUS 患者的癌症风险约为对照人群的 6.5 倍，可能会进展为 MGUS。多发性骨髓瘤 (MM)、华氏巨球蛋白血症 (WM)、非霍奇金淋巴瘤 (NHL)、慢性淋巴细胞白血病（CLL）、淀粉样轻链（AL）淀粉样变性或浆细胞瘤，大部分。 NHL、AL和淀粉样变性是不治之症，而CLL和浆细胞瘤则很少被治愈。 MGUS 呼吁建立专门针对这种癌前病变的癌症预防拦截 U54 专业中心病情 - MGUS 影响约 1% 的人口，MGUS 进展为癌症或其他相关血液疾病疾病持续以每年约 1% 的速度增长，约 90% 的 MGUS 进展为癌症/疾病所有 MGUS 患者都是癌症预防和拦截的潜在候选者。培育癌症驱动分子和促进 MGUS 的骨髓微环境我们建议设立癌症预防 - 阻止 MGUS 进展为癌症 (CAP-MGUS) 中心，是一个灵活、高效的中心该中心将建立致力于防止 MGUS 进展的有效网络基础设施。重点关注预防或拦截的免疫学和化学靶向药物的合作研究我们提出了三个目标来实现 MGUS 或闷烧性疾病患者的致癌过程。 CAP-MGUS 中心的总体目标是在目标 1 中，我们将对肿瘤中的多个癌靶点进行功能验证。侵袭性癌症的发生和进展，并确定其是否适合有针对性的干预策略。在目标 2 中，我们将通过体外发现创新的免疫和化学预防和拦截剂在目标 3 中，我们将通过确定癌症的新靶点来开发新项目。总的来说，我们期望获得针对 MGUS 进展的预防性或拦截性干预措施。用于进一步开发或早期临床试验的化学预防和免疫预防药物。