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）：根据美国癌症协会的说法，估计在2008年美国发生了182,000例侵入性乳腺癌病例，由于乳腺癌而导致40,000例死亡。在转移性乳腺癌的女性中，5年生存率为27％。在此SBIR I期应用中提出的研究旨在评估开发合成造菌素治疗乳腺癌的可行性。美国国家癌症研究所（National Cancer Institute）的工人分离了第一家天然产物家族的schweinfurthins，并显示出对乳房，白血病/淋巴瘤，肾脏，黑色素瘤和CNS Sub-Panels的非凡活性。 Schweinfurthins似乎具有新颖的作用机理，并且可以广泛适用于满足乳腺癌患者的大量未满足医疗需求。虽然最初在天然产品屏幕上发现，但这些化合物的自然来源仅提供少量，并且证明对重新隔离不可靠。爱荷华大学的Terpenoid Therapeutics及其合作者设计和合成了五十多种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莫尔效能的化合物。该阶段I可行性应用的目的是确定人类乳腺癌异种移植模型中合成造粉素的体内功效。该项目将通过两个具体目的来进一步开发合成造菌素，用于治疗乳腺癌：1）单独分析合成造粉菌，并与目前用于治疗乳腺癌的药物结合使用，用于乳腺癌的体外抑制人类乳腺癌细胞。线条和选择用于在体内功效模型中测试的化合物； 2）单独测试合成的schweinfurthin，并与乳腺癌异种移植模型中的标准疗法结合使用，以建立体内疗效。这些研究的数据将支持II期SBIR提案，以将合成的schweinfurthin推向辅助研究。 公共卫生相关性：尽管在转移性乳腺癌治疗方面取得了重要进展，但仍需要创新的新疗法。根据美国癌症协会的数据，2008年，美国发生了182,000例侵入性乳腺癌病例，由于乳腺癌而导致40,000例死亡。在转移性乳腺癌的女性中，5年生存率为27％。为了改善患者的结局，需要研究以鉴定转移性乳腺癌的新型治疗方法，例如合成造粉菌。