SPORE in Breast Cancer

乳腺癌中的孢子

• 批准号: 8250847
• 负责人: Laura J Van't Veer
• 金额: $ 230万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8250847
• 关键词: Address; Advocacy; Amplifiers; Apoptosis; Area; Bioinformatics; Biological Assay; Biometry; Clinical; Development; Disease; Event; FDA approved; Genomics; Human; Malignant Neoplasms; Molecular; Neoplasm Metastasis; Noninfiltrating Intraductal Carcinoma; Nucleic Acids; Outcome; Patients; Pharmaceutical Preparations; Phenotype; Premalignant; Recurrence; Risk; Small Interfering RNA; Stratification; Telomerase; Telomerase RNA Component; Testing; Therapeutic; Therapeutic Agents; Tissues; Translational Research; Woman; Work; base; chemotherapy; effective therapy; experience; high risk; improved; knock-down; malignant breast neoplasm; molecular marker; mutant; nanoparticle; response; telomere; tumor

The Bay Area Breast Cancer SPORE renewal application focuses on unmet needs in two areas - improved management of premalignant disease and more effective treatment of invasive cancer subtypes that do not respond well to current therapeutic strategies and that are at high risk of metastasis. Our approach is based on the increasingly well-established concept that breast cancer is a heterogeneous disease in which molecularly defined subsets progress and respond differentially to therapy. Work proposed in this renewal application will be carried out in four projects: Project 1 - Risk Stratification for Subsequent Tumors in Women with DCIS will test the hypothesis that the molecular events discovered to be important in early breast cancer development during the last project period will be associated with risk of subsequent progression of DCIS to invasive cancer. Project 2 - Genomic Approaches to Breast Cancer Subsets Identification and Treatment will identify FDA approved and experimental drugs that are effective against basal and luminal/amplifier breast cancer subtypes, develop molecular marker assays to guide the clinical introduction of these drugs and explore the molecular mechanisms through which effective drugs operate. Project 3 - Nanoparticle-based Chemotherapy against Aggressive Breast Cancer Subtypes will develop lipidic nanoparticle-based therapies immunologically targeted to aggressive breast cancer phenotypes, with particular emphasis on treatment of basal-like tumors. Project 4 - Breast Cancer Therapeutic Agents Based on Telomerase Misfunction will continue to develop a nucleic acid construct to knock down expression of endogenous human telomerase RNA (siRNA against hTer) and introduce mutant-template hTer (MT-hTer) to force synthesis of mutant telomeres thereby inducing a rapid DMA damage response with telomere uncapping and apoptosis. These projects will supported by cores for Administration, Tissue and Outcomes, Biostatistics, Bioinformatics. In addition, an Advocacy Core infuses relevant patient experiences into the SPORE, addresses recurrent barriers to translational research, and networks with various organizations throughout the Bay Area and nationally.

湾区乳腺癌 SPORE 更新应用程序侧重于两个领域未满足的需求 - 改善癌前疾病的管理和更有效地治疗对当前治疗策略反应不佳且转移风险较高的侵袭性癌症亚型。我们的方法基于日益成熟的概念，即乳腺癌是一种异质性疾病，其中分子定义的子集进展并对治疗产生不同的反应。本次更新申请中提出的工作将在四个项目中进行： 项目 1 - 患有导管原位癌 (DCIS) 的女性后续肿瘤的风险分层将测试以下假设：在上一个项目期间发现的对早期乳腺癌发展很重要的分子事件将被与 DCIS 随后进展为浸润性癌症的风险相关。项目 2 - 乳腺癌亚型识别和治疗的基因组方法将确定 FDA 批准的、可有效对抗基底型和管腔型/扩增型乳腺癌亚型的实验药物，开发分子标记测定法以指导这些药物的临床引入，并通过以下方式探索分子机制：哪些药物有效发挥作用。项目3——基于纳米粒子的侵袭性乳腺癌亚型化疗将开发基于脂质纳米粒子的疗法，在免疫学上针对侵袭性乳腺癌表型，特别强调基底细胞样肿瘤的治疗。项目4——基于端粒酶缺陷的乳腺癌治疗剂将继续开发核酸构建体，以敲低内源性人端粒酶RNA（针对hTer的siRNA）的表达，并引入突变模板hTer（MT-hTer）以强制突变端粒的合成从而诱导快速 DMA 损伤反应，导致端粒脱帽和细胞凋亡。这些项目将得到管理、组织和结果、生物统计学、生物信息学核心的支持。此外，倡导核心将相关患者经验融入 SPORE，解决转化研究中经常出现的障碍，并与整个湾区和全国范围内的各个组织建立联系。

项目成果

Reconstructing Tumor Genome Architectures

重建肿瘤基因组架构

• 发表时间: 1970-01-01
• 作者: M. Strauch

Identification and characterization of tumor antigens by using antibody phage display and intrabody strategies.

使用抗体噬菌体展示和体内策略鉴定和表征肿瘤抗原。

• DOI: 10.1016/j.molimm.2007.03.023
• 发表时间: 2007-07-01
• 期刊: Molecular immunology
• 影响因子: 3.6
• 作者: A. Goenaga;Yu Zhou;C. Legay;H. Bougherara;Lan Huang;B. Liu;D. Drummond;D. Kirpotin;C. Auclair;J. Marks;M. Poul
• 通讯作者: M. Poul

Incidence of and treatment for ductal carcinoma in situ of the breast.

乳腺导管原位癌的发病率和治疗。

• 发表时间: 1996-03-27
• 作者: Ernster, V L;Barclay, J;Kerlikowske, K;Grady, D;Henderson, C
• 通讯作者: Henderson, C

Assessing tumor angiogenesis using macromolecular MR imaging contrast media.

使用大分子磁共振成像造影剂评估肿瘤血管生成。

• 发表时间: 1997-01
• 作者: Brasch, R;Pham, C;Shames, D;Roberts, T;van Dijke, K;van Bruggen, N;Mann, J;Ostrowitzki, S;Melnyk, O
• 通讯作者: Melnyk, O

Immunoliposomes for cancer treatment.

用于癌症治疗的免疫脂质体。

• 发表时间: 1997
• 作者: Park, J W;Hong, K;Kirpotin, D B;Papahadjopoulos, D;Benz, C C
• 通讯作者: Benz, C C