Translational Research in Breast Cancer

摘要 转移性乳腺癌的治疗缺乏进展是由于一些基本的治疗障碍。这些 包括对治疗弱点认识不足、缺乏可靠的预测生物标志物、不能 靶向常见肿瘤抑制基因缺失，不能靶向不是蛋白激酶或配体的癌基因， 依赖性转录因子，由于克隆进化和肿瘤异质性而产生的抗性，以及未能安装 对肿瘤的免疫反应这次SPORE更新的重点是通过阐明跨- 削减目标和协调一致的方法，提高核心资源利用效率，促进项目间合作， 协作这三个完整的项目包括研究如何靶向去抑制激酶， 乳腺癌中PTPN 12或NF 1肿瘤抑制因子的缺失，以及一种有前途的新的 MYC阳性乳腺癌的治疗方法。在执行这些项目期间，我们将：a）部署 用于监测激酶靶标和抗性途径的蛋白基因组学方法; B）建立高质量的 用于临床试验合格性和分层的生物标志物; c）研究疾病监测方法， 循环肿瘤细胞（CTC）和循环肿瘤DNA（ctDNA）; d）结合免疫学方法 通过增加肿瘤浸润淋巴细胞的质量和数量，将我们的研究纳入治疗方案; 将SPORE生物标志物计划纳入早期临床试验，为3期试验的设计提供信息;以及f）促进 学术界、NCI-Supported Cooperative Groups、工业界和倡导者之间的合作研究 组 这些目标是由三个重新格式化的核心，加上一个专门的和高素质的 病理学和生物库核心的分子研究病理学家，增加了更深层次的生物信息学 信息学和生物统计学核心的专业知识，以及一个新的SPORE主任加上其他倡导者， 行政核心的顾问委员会成员。职业提升与发展研究 项目将由经验丰富的领导层指导，并将一如既往地巩固我们SPORE的未来。 有了这个强大的增强计划，我们将在全国范围内倡导在治疗晚期乳腺癌方面取得进展。 乳腺癌，相信治愈是一个短期的可能性。

Abstract Lack of progress in curing metastatic breast cancer is due to a number of fundamental treatment barriers. These include insufficient knowledge of therapeutic vulnerabilities, lack of reliable predictive biomarkers, inability to target common tumor suppressor gene loss, inability to target oncogenes that are not protein kinases or ligand- dependent transcription factors, resistance due to clonal evolution and tumor heterogeneity, and failure to mount an immune response against the tumor. This SPORE renewal focuses on these obstacles by articulating cross- cutting objectives and aligned approaches that increase the efficiency of core utilization and promote inter-project collaboration. The three full Projects include studies on how to target the derepressed kinases consequent upon loss of the PTPN12 or the NF1 tumor suppressors in breast cancer, and the development of a promising new therapeutic approach for MYC-positive breast cancer. During the execution of these Projects we will: a) deploy proteogenomic approaches for monitoring kinase targets and resistance pathways; b) establish high-quality biomarkers for clinical trial eligibility and stratification; c) investigate disease-monitoring approaches with circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA); d) incorporate immunological approaches into treatment regimens by increasing the quality and quantity of tumor infiltrating lymphocytes; e) embed our SPORE biomarker program into early phase clinical trials to inform the design of Phase 3 trials; and f) promote collaborative research between Academia, NCI-Supported Cooperative Groups, Industry, and Advocacy Groups. These objectives are served by three reformatted Cores, with the addition of a dedicated and highly-qualified molecular research pathologist for the Pathology and Biobanking Core, the addition of deeper bioinformatics expertise to the Informatics and Biostatistics Core, and a new SPORE director plus additional advocates and advisory board members for the Administration Core. The Career Enhancement and Developmental Research Programs will be guided by highly experienced leadership and, as before, will cement the future of our SPORE. With this powerful enhanced program we will advocate nationally for progress in the treatment of advanced breast cancer, with the conviction that a cure is a near-term possibility.