Probes targeting multiple myeloma in the context of tumor-stromal interactions

在肿瘤-基质相互作用的背景下针对多发性骨髓瘤的探针

• 批准号: 8590942
• 负责人: Douglas McMillin
• 金额: $ 28.87万
• 依托单位: AXIOS BIOSCIENCES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-09 至 2015-09-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8590942
• 关键词: Affect; Biological Assay; Bone Marrow; Cancer cell line; Cell Communication; Cells; Characteristics; Chemicals; Clinic; Collaborations; Collection; Dana-Farber Cancer Institute; Data; Exhibits; FDA approved; Funding Opportunities; Future; Generations; Genetic; Genomics; Health; Human; In Vitro; Lesion; Luciferases; Malignant Neoplasms; Marketing; Medical Research; Multiple Myeloma; Nature; Neoplasm Metastasis; Neoplasms; Non-Malignant; Patients; Performance; Pharmaceutical Preparations; Phase; Pre-Clinical Model; Principal Investigator; Publishing; Research Institute; Research Personnel; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Stromal Cells; Stromal Neoplasm; System; Technology; Testing; Therapeutic; Tissues; Translations; Tumor Cell Invasion; Tumor Cell Line; Tumor Tissue; Validation; bone; drug discovery; drug market; high throughput screening; medical schools; mouse model; neoplastic cell; novel; programs; response; screening; technical report; tumor; tumor microenvironment

DESCRIPTION (provided by applicant): This Small Business Innovation Research (SBIR) Phase I application is in response to Funding Opportunity Announcement PA-12-088. Tumor-stromal interactions are increasingly recognized as critical components of the progression of human neoplasias, including tumor invasion and metastasis. Utilizing a novel high- throughput screening approach developed by the applicants, compounds will be identified having superior anti- myeloma activity in the presence of bone marrow stromal cells. This system more closely replicates the interactions of tumors and non-malignant tissues in patients, allowing the discovery of more clinically effective therapeutics compared to cell autonomous approaches. This proposal, in collaboration with the Conrad Prebys Center for Chemical Genomics (CPCCG) at Sanford-Burnham Medical Research Institute, focuses on screening a large compound collection against multiple myeloma cancer cell lines in the presence and absence of non-malignant bone marrow stromal cells to identify compounds with superior activity in a tumor microenvironment context. Probes will be further evaluated against a larger panel of tumors and non-malignant stromal cells to examine their broader activity. This technology and approach is a revolutionary advancement over current cell autonomous systems and has the potential to identify new first-in-class, FDA-approved and marketed drugs missed using conventional drug discovery approaches.

描述（由申请人提供）：此小型企业创新研究（SBIR）第一阶段申请是对资助机会公告PA-12-088的回应。肿瘤间质相互作用越来越被认为是人类肿瘤进展的关键组成部分，包括肿瘤侵袭和转移。利用本申请人开发的新的高通量筛选方法，将鉴定在骨髓基质细胞存在下具有上级抗骨髓瘤活性的化合物.该系统更紧密地复制了患者中肿瘤和非恶性组织的相互作用，与细胞自主方法相比，可以发现临床上更有效的治疗方法。该提案与Sanford-Burnham医学研究所的Conrad Prebys化学基因组学中心（CPCCG）合作，重点是在存在和不存在非恶性骨髓基质细胞的情况下筛选针对多发性骨髓瘤癌细胞系的大型化合物集合，以鉴定在肿瘤微环境中具有上级活性的化合物。将针对更大的肿瘤和非恶性基质细胞组进一步评价探针，以检查其更广泛的活性。这种技术和方法是对当前细胞自主系统的革命性进步，并有可能识别出使用传统药物发现方法错过的新的一流的、FDA批准和上市的药物。