Novel Treatment for Breast Cancer: Truncated Galectin-3

乳腺癌的新疗法：截短的半乳糖凝集素 3

• 批准号: 6489447
• 负责人: Constance M John
• 金额: $ 25.55万
• 依托单位: MANDALMED, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-10 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6489447
• 关键词: antineoplastics; breast neoplasms; collagenase; drug screening /evaluation; histopathology; laboratory mouse; lectin; neoplasm /cancer chemotherapy; protein engineering; tissue /cell culture

DESCRIPTION (provided by applicant): Despite the available treatments breast cancer ranks second as the cause of death from cancer in women primarily due to metastases of the primary tumor to other sites in the body. We will extend our preliminary study of the anticancer activity of recombinant human galectin-3 N-terminally truncated by collagenase in an orthotopic mouse model of metastatic breast cancer. We postulate that galectin-3 truncated by collagenase blocks the binding sites for galectin-3 and prevent its cell crosslinking and other activities. We will determine the in vivo efficacy of an analogous galectin-3 variant (delta 107) produced in E. coli and compare it with that of galectin-3 truncated enzymatically. We will perform a dose-response analysis to firmly establish the activity of the delta 107 variant, and address the optimal dose. We will also test the anticancer activity of a slightly longer mutant of galectin-3. A series of cell-based assays would be used to compare the in vitro activities of the galectin-3 variants with intact galectin-3. Further development of truncated galectin-3 as a clinical candidate for breast cancer would be the focus of the Phase II research. PROPOSED COMMERCIAL APPLICATION: An estimated 40,800 Americans are expected to die of breast cancer this year. A therapy that primarily acts to reduce metastasis could be effective in treating breast cancer, especially early stage cancer. If galectin-3 has a reduced incidence of side effects this would increase its attractiveness. The commercial potential of breast cancer therapeutics is large.

描述（由申请人提供）： 尽管有可用的治疗方法，乳腺癌仍然排名第二 癌症死亡的妇女死亡主要是由于原发性肿瘤的转移 体内的其他部位。 我们将扩展我们对 重组人半乳糖素-3 N末端的抗癌活性，被截断 在转移性乳腺癌的原位小鼠模型中的胶原酶。 我们假设通过胶原酶截断的乳糖素3阻断结合位点 对于Galectin-3，并防止其细胞交联和其他活动。 我们 将确定类似lectectin-3变体的体内疗效（delta 107）在大肠杆菌中产生，并将其与Galectin-3的截短 酶上。 我们将执行剂量反应分析以牢固建立 增量107变体的活性，并解决最佳剂量。 我们将 还可以测试半乳糖素3突变体的抗癌活性。 一系列基于细胞的测定将用于比较体外活性 具有完整lectectin-3的Galectin-3变体的。 进一步发展 截短的Galectin-3作为乳腺癌的临床候选者将是 第二阶段研究的重点。 拟议的商业应用： 预计今年有40,800名美国人将死于乳腺癌。 一个 主要起作用转移的治疗可能有效地治疗乳房 癌症，尤其是早期癌症。 如果Galectin-3的发生率降低 效果这将提高其吸引力。 乳房的商业潜力 癌症治疗剂很大。