Project 3: Systematic characterization of factors controlling breast cancer progression and resistance

项目3：控制乳腺癌进展和耐药因素的系统表征

• 批准号: 10911510
• 负责人: MICHAEL C BASSIK
• 金额: $ 6.62万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-14 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10911510
• 关键词: Breast Cancer Cell; Breast Cancer cell line; CRISPR interference; CRISPR screen; Cancer Model; Cell Communication; Development; Drug Targeting; Drug resistance; Effectiveness; Estrogen receptor positive; Growth; Immune system; In Vitro; Macrophage; Magnetism; Malignant Neoplasms; Metastatic breast cancer; Neoplasm Metastasis; Phagocytosis; Phenotype; Property; Resistance; Resistance development; System; breast cancer progression; cancer cell; cancer therapy; genome-wide; hormone therapy; in vivo; neoplastic cell; parent grant; relapse risk; targeted treatment; three dimensional cell culture; tumor; tumor microenvironment

Summary of the Parent Grant Project 3: Systematic characterization of factors controlling breast cancer progression and resistance Two central challenges limit effectiveness of cancer therapies and enable metastasis: development of intrinsic resistance to targeted drugs, and development of resistance to recognition and destruction of cancer cells by the immune system. Traditional in vitro cancer models have been limited in scale and often lack key properties of the tumor microenvironment. We recently developed a scalable cancer spheroid system that enabled the first genome-wide CRISPR screens in 3D culture; phenotypes in this system much better reflect in vivo tumors (Han et al., 2020). In addition, we developed a magnetic separation strategy to rapidly identify regulators of phagocytosis by macrophages (Haney et al., 2018), and have successfully extended this strategy to study macrophage-tumor cell interactions. Here we propose to use these systems to identify regulators of resistance to targeted and endocrine therapies and macrophage killing in metastatic breast cancer. Aim 1: Identify critical drivers of growth and drug resistance in high relapse risk ER+ breast cancer cell lines and PDOs using CRISPRi/a screen Aim 2: Systematic identification and characterization of factors limiting macrophage phagocytosis of breast cancer cells

家长资助项目3的总结：控制乳房的因素的系统表征