SPORE in Breast Cancer

乳腺癌中的孢子

• 批准号: 8039212
• 负责人: Laura J Van't Veer
• 金额: $ 190.23万
• 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 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8039212
• 关键词: SPORE; Breast; Cancer

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-改善癌前病变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高的浸润性癌症亚型。我们的方法是基于日益完善的概念，乳腺癌是一种异质性疾病，其中分子定义的子集的进展和治疗反应差异。本延续申请中提出的工作将在四个项目中进行：项目1 -DCIS女性后续肿瘤的风险分层将检验以下假设：在上一个项目期间发现的在早期乳腺癌发展中重要的分子事件将与DCIS后续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识别FDA批准的和实验性药物，这些药物对基底和腔/放大乳腺癌亚型有效，开发分子标记物测定来指导这些药物的临床引入，并探索有效药物的分子机制发挥作用。项目3 -针对侵袭性乳腺癌亚型的基于纳米颗粒的化疗将开发免疫靶向侵袭性乳腺癌表型的基于纳米颗粒的治疗方法，特别强调基底样肿瘤的治疗。项目4 -基于端粒酶功能失调的乳腺癌治疗剂将继续开发一种核酸构建体，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），以强制合成突变端粒，从而诱导快速的DNA损伤反应，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，一个倡导核心注入相关的病人经验到孢子，解决转化研究的经常性障碍，并与整个湾区和全国的各种组织网络。