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，乳腺癌仍是第二大病因。 女性癌症死亡主要是由于原发肿瘤转移到 身体的其他部位。 我们将扩大我们的初步研究 N-末端截短的重组人半乳糖凝集素-3的抗癌活性 转移性乳腺癌原位小鼠模型中的胶原酶。 我们推测胶原酶截短的半乳糖凝集素-3阻断了结合位点 并阻止其细胞交联等活性。 我们 将确定类似的半乳糖凝集素-3变体（δ 107)在E.并与半乳糖凝集素-3截短体进行比较 酶促地。 我们将进行剂量反应分析， Δ 107变体的活性，并确定最佳剂量。 我们将 还测试了半乳糖凝集素-3的稍长突变体的抗癌活性。 一系列基于细胞的测定将用于比较体外活性 半乳糖凝集素-3变体与完整的半乳糖凝集素-3。 进一步发展 截短的半乳糖凝集素-3作为乳腺癌的临床候选者将是 第二阶段研究的重点。 拟定商业应用： 预计今年将有40,800名美国人死于乳腺癌。 一 主要用于减少转移的疗法可有效治疗乳腺癌， 癌症，尤其是早期癌症。 如果半乳糖凝集素-3具有降低的副作用发生率， 这将增加它的吸引力。 乳房的商业潜力 癌症治疗是很大的。