Validation of HMGI-C as a Drug Target in Colon Cancer

HMGI-C 作为结肠癌药物靶点的验证

• 批准号: 6551961
• 负责人: ROLAND A CHOUINARD
• 金额: $ 9.79万
• 依托单位: HMGENE, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6551961
• 关键词: adenomatous polyps; antineoplastics; antisense nucleic acid; colon neoplasms; drug design /synthesis /production; drug metabolism; genetically modified animals; laboratory mouse; neoplasm /cancer genetics; neoplastic transformation; transcription factor

DESCRIPTION (provided by applicant): Colon cancer is a major health concern of the United States, with an estimated 129,400 new cases reported in 1999. Colon cancer is now the second leading cancer killer of both men and women in the U.S. after lung cancer. The successful management of this disease will require the discovery of safe and effective pharmacological agents. The goal of the present proposal is to validate HMGI-C (High Mobility Group I-C), an architectural transcription factor which regulates gene expression in tumorigenesis, as a drug target for colon cancer. The experimental approach will involve the inactivation of HMGI-C in Min mice, a widely accepted model of colon cancer resulting from an ethylnitrosurea (ENU) induced nonsense mutation at codon 850 of the murine Apc (adenomatous polyposis coli) gene. Germline mutations in humans in the APC gene are responsible for familial adenomatous polyposis, an inherited form of colon cancer. APC gene defects are also highly prevalent in sporadic colon tumors. It is hoped that inactivation of HMGI-C will attenuate colon cancer by inhibiting tumor formation or progression, thus validating HMGI-C as a drug target for colon cancer and setting the stage for a Phase II investigation into possible drug discovery. PROPOSED COMMERCIAL APPLICATION: Successful completion of this project would open up new prospects for the discovery of effective, clinically valuable drugs for the treatment of colon cancer which would have an enormous commercial potential. It is now estimated that in the United States alone, 129,400 new cases of colon cancer were reported, indicating the demand for safe, reliable pharmaceuticals.

描述（由申请人提供）：结肠癌是美国的一个主要健康问题，1999 年估计报告了 129,400 个新病例。结肠癌现在是美国男性和女性的第二大癌症杀手，仅次于肺癌。成功治疗这种疾病需要发现安全有效的药物。本提案的目标是验证 HMGI-C（高迁移率组 I-C）作为结肠癌的药物靶点，HMGI-C 是一种调节肿瘤发生中基因表达的结构转录因子。 该实验方法将涉及 Min 小鼠中 HMGI-C 的失活，Min 小鼠是一种广泛接受的结肠癌模型，由乙基亚硝基脲 (ENU) 诱导的小鼠 Apc（腺瘤性息肉病大肠杆菌）基因密码子 850 处的无义突变引起。人类 APC 基因种系突变导致家族性腺瘤性息肉病，这是一种遗传性结肠癌。 APC 基因缺陷在散发性结肠肿瘤中也非常普遍。希望 HMGI-C 失活能够通过抑制肿瘤形成或进展来减弱结肠癌，从而验证 HMGI-C 作为结肠癌的药物靶点，并为可能的药物发现的 II 期研究奠定基础。 拟议的商业应用： 该项目的成功完成将为发现有效的、有临床价值的治疗结肠癌药物开辟新的前景，并具有巨大的商业潜力。 据估计，仅在美国就报告了 129,400 例结肠癌新病例，表明对安全、可靠的药品的需求。