Cancer Prevention-Interception Against MGUS Progression

癌症预防——阻止 MGUS 进展

• 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
• 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' 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

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.

项目摘要 不确定意义（MGU）的单克隆性γ- 血液中异常免疫球蛋白（Ig）蛋白（称为M蛋白）的水平适度升高。 MGUS患者的癌症风险约为对照人群的6.5倍。 MGU可能会发展 多发性骨髓瘤（MM），Waldenström巨球素血症（WM），非霍奇金淋巴瘤（NHL），慢性 淋巴细胞性白血病（CLL），淀粉样轻链（AL）淀粉样变性或可塑性瘤。 MM，WM，大部分 NHL和Al淀粉样变性是无法治愈的疾病。 CLL和浆细胞瘤很少治愈。意义 Mgus呼吁进行预防癌症截断U54专用中心 条件MGU会影响约1％的人口，MGUS发展为癌症或其他相关的血液 疾病持续以每年约1％的速度，而从mgus进行的癌症/疾病〜90％ 无法治愈。所有MGU患者都是预防癌症和拦截的潜在候选者。我们 假设癌症驱动分子和骨髓微环境促进mgus 进展是用于预防癌症和拦截的合适目标。我们建议建立 针对MGUS进展到癌症（CAP-MGU）中心的癌症预防疗法作为敏捷和 有效的网络基础架构致力于预防MGUS的进展。这个中心将承担 侧重于免疫学和化学靶向药物的协作研究，以预防或拦截 MGU或闷烧疾病患者的致癌过程。我们提出三个目标以实现 Cap-Mgus中心的总体目标。在AIM 1中，我们将在功能上验证肿瘤中的几个Oncotargets 起步和进展为侵入性癌症，并确定其对有针对性干预策略的适用性。 在AIM 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 和体内效率评估。在AIM 3中，我们将通过确定癌症的新目标来开发新项目 - 针对MGUS进展的预防或拦截干预措施。我们希望获得 用于进一步开发或早期临床试验的化学预防和免疫预防剂。