Schweinfurthins: novel treatment for breast cancer

Schweinfurthins：乳腺癌的新疗法

• 批准号: 7798657
• 负责人: JEFFREY D NEIGHBORS
• 金额: $ 20.4万
• 依托单位: TERPENOID THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-11 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7798657
• 关键词: Address; Advocate; American Cancer Society; Antitumor Drug Screening Assays; Biological Assay; Biological Factors; Breast; Breast Cancer Cell; Breast Cancer Treatment; Cancer cell line; Cell Line; Central Nervous System Melanoma; Cessation of life; Collaborations; Data; Development; Disease; Evaluation; Family; Funding; Goals; Grant; Growth; Human; In Vitro; Iowa; Kidney; Legal patent; Medical; Modeling; National Cancer Institute; Outcome; Patients; Pharmaceutical Preparations; Phase; Research; Small Business Innovation Research Grant; Source; Survival Rate; Terpenes; Testing; Therapeutic; Tumor Cell Line; Universities; Woman; Work; Xenograft Model; analog; cancer type; design; experience; improved; in vitro activity; in vivo; innovation; leukemia/lymphoma; malignant breast neoplasm; novel; public health relevance

DESCRIPTION (provided by applicant): According to the American Cancer Society an estimated 182,000 cases of invasive breast cancer occurred in the US in 2008, with 40,000 deaths due to breast cancer. Among women with metastatic breast cancer, the 5-year survival rate is 27%. The studies proposed in this SBIR phase I application are designed to assess the feasibility of developing synthetic schweinfurthins for the treatment of breast cancer. The first schweinfurthins from a family of natural products were isolated by workers at the National Cancer Institute and showed remarkable activity against the breast, leukemia/lymphoma, renal, melanoma and CNS sub-panels of the NCI 60-cell line bioassay. The schweinfurthins appear to have a novel mechanism of action and could have broad applicability to address the significant unmet medical need of patients with breast cancer. While initially discovered during a natural products screen, the natural sources of these compounds supply only small amounts and have proven unreliable for re-isolation. Terpenoid Therapeutics and its collaborators at the University of Iowa have designed and synthesized over fifty schweinfurthin analogues, including several compounds which have low nanomolar potency against human breast cancer cell lines in vitro. The goal of this phase I feasibility application is to establish in vivo efficacy of synthetic schweinfurthins in human breast cancer xenograft models. This project will undertake the further development of synthetic schweinfurthins for the treatment of breast cancer through two specific aims: 1) Analyze synthetic schweinfurthins alone and in combination with drugs currently used in the treatment of breast cancer for in vitro growth inhibition of human breast cancer cell lines and select compounds for testing in in vivo efficacy models; and 2) Test a synthetic schweinfurthin alone and in combination with standard therapies in breast cancer xenograft models to establish in vivo efficacy. The data from these studies will support a Phase II SBIR proposal to advance a synthetic schweinfurthin into IND-enabling studies. PUBLIC HEALTH RELEVANCE: In spite of important advances in the treatment of metastatic breast cancer, there remains a need for innovative new therapies. According to the American Cancer Society an estimated 182,000 cases of invasive breast cancer occurred in the US in 2008, with 40,000 deaths due to breast cancer. Among women with metastatic breast cancer, the 5-year survival rate is 27%. Research to identify novel treatments for metastatic breast cancer, such as the synthetic schweinfurthins, is needed to improve the outcomes for patients.

描述（由申请人提供）：据美国癌症协会估计，2008 年美国发生了 182,000 例浸润性乳腺癌，其中 40,000 人死于乳腺癌。患有转移性乳腺癌的女性的 5 年生存率为 27%。 SBIR I 期申请中提出的研究旨在评估开发合成猪威辛治疗乳腺癌的可行性。美国国家癌症研究所的工作人员从一个天然产品家族中分离出了第一个猪肝素，并在 NCI 60 细胞系生物测定中显示出对乳腺癌、白血病/淋巴瘤、肾病、黑色素瘤和中枢神经系统亚组的显着活性。猪肝素似乎具有新颖的作用机制，并且具有广泛的适用性，可以解决乳腺癌患者未得到满足的重大医疗需求。虽然最初是在天然产品筛选过程中发现的，但这些化合物的天然来源仅提供少量，并且已证明重新分离不可靠。 Terpenoid Therapeutics 及其在爱荷华大学的合作者设计并合成了 50 多种 schweinfurthin 类似物，其中包括几种在体外对人类乳腺癌细胞系具有低纳摩尔效力的化合物。这一阶段的可行性应用的目标是确定合成猪瘟在人乳腺癌异种移植模型中的体内功效。该项目将通过两个具体目标进一步开发用于治疗乳腺癌的合成猪瘟素：1）单独分析合成猪瘟素以及与目前用于治疗乳腺癌的药物联合使用对人乳腺癌细胞系的体外生长抑制作用，并选择化合物用于测试体内功效模型； 2) 在乳腺癌异种移植模型中单独测试合成猪瘟素以及与标准疗法组合，以确定体内疗效。这些研究的数据将支持 II 期 SBIR 提案，将合成猪威辛推进 IND 研究。 公共卫生相关性：尽管转移性乳腺癌的治疗取得了重要进展，但仍然需要创新的新疗法。据美国癌​​症协会估计，2008 年美国发生了 182,000 例浸润性乳腺癌，其中 40,000 人死于乳腺癌。患有转移性乳腺癌的女性的 5 年生存率为 27%。需要进行研究来确定转移性乳腺癌的新疗法，例如合成猪瘟，以改善患者的治疗结果。