权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer

丹娜—法伯癌症研究所/哈佛大学癌症中心 SPORE 在乳腺癌中的应用

基本信息

批准号：
10215406
负责人：
NANCY U LIN
金额：
$ 234.53万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-17 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10215406
关键词：
Address Award Biological Biological Assay Biological Testing Biology Biometry Biopsy Blood Breast Cancer Treatment Breast Cancer therapy Bromodomain CDK2 gene CDK4 gene Cancer Biology Cancer Center Cancer Patient Chloroquine Clinic Clinical Clinical Data Clinical Investigator Clinical Research Clinical Trials Clinical Trials Cooperative Group Collaborations Collection Combined Modality Therapy Communication Complement Computational Biology Dana-Farber Cancer Institute Data Development Disease ERBB2 gene Ensure Estrogen receptor positive Funding Future General Hospitals Goals Growth Hospitals Human Immune Evasion Immune system Immunology Immunooncology Immunotherapy Individual Institution International Investigation Israel Laboratories Laboratory Research Lead Massachusetts Medical center Mentors Metastatic Neoplasm to the Central Nervous System Metastatic malignant neoplasm to brain Methods Morbidity - disease rate Mus Neoplasm Metastasis Pathology Pathway interactions Patient advocacy Patients Pharmacology Pre-Clinical Model Premature Mortality Randomized Regimen Research Research Personnel Research Project Grants Resected Resistance Resistance development Resources Role Running Services Site Structure Systemic Therapy Testing Tissues Translating Translational Research Treatment Efficacy Triad Acrylic Resin Woman Work Xenograft procedure anti-tumor immune response base biomarker discovery cancer immunotherapy cancer subtypes career co-clinical trial experience experimental study genomic data immune checkpoint blockade improved inhibitor/antagonist innovation insight malignant breast neoplasm molecular subtypes next generation novel novel strategies novel therapeutic intervention patient population pre-clinical preclinical study programmed cell death ligand 1 programs repository resistance mechanism symposium targeted treatment therapy resistant translational approach translational impact translational scientist triple-negative invasive breast carcinoma tumor tumor immunology tumor-immune system interactions

项目摘要

PROJECT SUMMARY The Dana-Farber/Harvard Cancer Center (DF/HCC) SPORE in Breast Cancer seeks to improve the understanding and treatment of breast cancer using an innovative and highly translational approach. The application consists of four projects, three cores, a developmental research program (DRP) and a career enhancement programs (CEP). Each project addresses a fundamental challenge that results in premature mortality or substantial morbidity. Project 1 brings together outstanding investigators to study mechanisms of resistance to CDK4/6 inhibitors. In estrogen receptor-positive breast cancer, we hypothesize that CDK2 hyperactivation is a cause of acquired resistance to CDK4/6 inhibitors. Elegant preclinical work will be complemented by a clinical study in which paired biopsies are obtained prior to initiation of CDK4/6 inhibitors and when resistance develops. In triple-negative breast cancer, we will evaluate the possibility that lysosomal sequestration of CDK4/6 inhibitors limits their therapeutic efficacy. In preclinical work, we will determine if this sequestration can be reversed administering chloroquine and will also conduct a trial of palbociclib/chloroquine in RB-intact triple-negative disease. Project 2 uses two “co-clinical” trials – running randomized human trials and mouse experiments largely in parallel – to study two novel therapeutic approaches to enhance the anti- tumor immune response against HER2-positive breast cancers (CDK4/6 inhibition and dual PDL1 and 4-1BB targeting). Both approaches are based on our compelling preclinical data, and will include local and international collaborators. Project 3 tackles the challenge of breast cancer brain metastases. Leveraging our unique collection of xenografts derived from resected human brain metastases, and our experience conducting brain metastasis-specific trials, we will test the biologic and clinical impact of two novel systemic therapy regimens. Project 4 is focused on triple-negative breast cancer. We will perform comprehensive preclinical studies and clinical trials to determine whether targeted therapies can sensitize triple-negative tumors to immunotherapy. We will evaluate combinations of either PARP inhibitors or BET bromodomain inhibitors with immune checkpoint blockade. Core A, the Administrative Core, is the epicenter of scientific, fiscal and administrative oversight. It will lead efforts in planning and communication, and also houses the Patient Advocacy Committee. Core A will ensure that existing DF/HCC structures support the SPORE clinical research efforts. Core B, the Biostatistics and Computational Biology core, provides specialized expertise in biostatistics and management of genomic data. Core C, the Biospecimen and Pathology Core, will maintain tissue/blood repositories for the SPORE projects and for investigators outside of the SPORE. It also provides critical pathology services for the projects and will perform cutting edge assays. Core C also houses the Immuno-Oncology Sub Core. The DRP and CEP identify novel approaches to translational questions in breast cancer and support young investigators. Our SPORE in Breast Cancer is poised to make substantial contributions over the next five years and beyond.

项目总结