Clinical Investigations and Precision Therapeutics

临床研究和精准治疗

基本信息

批准号：
9889067
负责人：
Janice M. Mehnert
金额：
$ 2.96万
依托单位：
RBHS -CANCER INSTITUTE OF NEW JERSEY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9889067
关键词：
Achievement Apoptosis Apoptotic Autophagocytosis BCL2 gene BRAF gene BRCA1 gene Back Basic Science Biological Markers Biological Specimen Banks Biomedical Engineering Biometry Cancer Center Cancer Center Support Grant Cancer Control Cancer Vaccines Cell Cycle Checkpoint Cell Death Cell Survival Clinic Clinical Clinical Data Clinical Protocols Clinical Research Clinical Trials Collaborations Computer Analysis DNA Polymerase II DNA Repair Development Early treatment Elderly Endometrial Carcinoma Estrogen receptor positive Fowlpox Funding Genes Genomic Instability Genomics Goals Grant Growth Histology Human Image Immune checkpoint inhibitor Immunooncology Immunotherapy Individual Inhibition of Apoptosis Institution Investigation MAP Kinase Gene Malignant Neoplasms Malignant neoplasm of pancreas Medical Oncology Mental disorders Merkel cell carcinoma Modeling Molecular Molecular Biology Molecular Conformation Mutation Oncogenic Viruses Oncolytic Outcome Paper Pathway interactions Patients Peer Review Grants Platinum Compounds Population Population Sciences Positioning Attribute Pre-Clinical Model Precision therapeutics Prevention Program Development Publications Publishing Radiation Oncology Research Research Personnel Resistance Resource Sharing Sampling Schools Science Screening for cancer Services Skin Cancer Solid Neoplasm Surgical Oncology Systems Biology TP53 gene Therapeutic Therapeutic Human Experimentation Translating Translational Research Translations Vaccines Virus Work advanced disease base bench to bedside biomarker development biomedical informatics cancer genetics cancer pharmacology cancer prevention cancer therapy checkpoint inhibition checkpoint therapy clinical development clinical investigation clinical translation combinatorial data management digital early phase clinical trial early phase trial experience histological image imaging approach immunoregulation individualized medicine inhibitor/antagonist malignant breast neoplasm meetings member mouse model multidisciplinary mutant novel novel diagnostics novel marker novel strategies novel therapeutic intervention novel therapeutics product development programs rare cancer resistance mechanism response response biomarker statistics targeted treatment therapeutic target translational clinical trial translational impact tumor tumor metabolism

项目摘要

CLINICAL INVESTIGATIONS AND PRECISION THERAPEUTICS PROJECT SUMMARY/ABSTRACT The overall goals of the Clinical Investigations and Precision Therapeutics (CIPT) Program are to translate outstanding science into early phase trials, to develop new diagnostic, prevention, and therapeutic strategies for human cancer, and to promote bidirectional translation from bench to bedside and back. CIPT provides a translational bridge between the basic science and population science programs and the clinic, and conducts its own programmatically aligned translational research. CIPT is unique in its centralization of experience in the development of early phase clinical trials with expertise in molecular biology, genomics, imaging analysis, systems biology, statistics, and biomarker development. CIPT members translate scientific findings to create new paradigms at the bench and in the clinic, and are positioned within this multidisciplinary framework to access the expertise necessary for high impact translational research. High impact translational projects are prioritized for institutional support. CIPT has 60 members from 22 Departments and 7 Schools. CIPT research is well funded with $5.6M annual direct peer-reviewed grant support, $4.4M of which is cancer- focused (9 multi-PI), with $2.3M from the NCI (8 R01-equivalent/7 PIs, one UM1). In the last funding period CIPT members published 929 papers, 42% of which were collaborative (29% intra- and 25% inter- collaborations) with 51% collaborative with other institutions. This represents an increase in both total and collaborative publications compared with last project period. Impactful science includes discovery of compounds that reactivate specific conformational mutants of p53 in collaboration with the Cancer Pharmacology Program (CP); development of rational combinations of MAPK pathway and apoptosis inhibition, and targeting cancer metabolism by inhibiting autophagy in collaboration with the Cancer Metabolism and Growth Program, (CMG); and identification of mechanisms of resistance to PARP inhibitors in BRCA1 mutant cancers in collaboration with Genome Instability and Cancer Genetics Program (GICG). These approaches are being assessed in the clinic and in mouse models. CIPT investigators worked with CMG and GICG investigators to identify novel markers of response to immune checkpoint therapy, including presence of DNA polymerase-epsilon mutations in endometrial cancer. Collaboration with biomedical engineers in CP led to development of a classifier to help guide treatment of early stage ER+ breast cancer based on computational analysis of digital histology images. Collaboration with the Cancer Prevention and Control Program (CPC) led to studies evaluating the impact of mental illness on breast cancer outcome in the elderly. Finally, clinical investigation of immune checkpoint therapy in Merkel cell carcinoma led to FDA approval of avelumab for advanced disease. CIPT science is fueled by translation of findings in the Research Programs, and reverse translation of clinical findings to identify novel molecular mechanisms of response and resistance. CPC, Part I: Narrative, Page 1 of 1; DRAFT 1/19/18 11:56 AM

临床研究和精准治疗项目概要/摘要临床研究和精准治疗 (CIPT) 计划的总体目标是将将杰出的科学纳入早期试验，以开发新的诊断、预防和治疗策略用于人类癌症，并促进从工作台到床边和返回的双向翻译。 CIPT 提供了基础科学和人口科学项目与临床之间的转化桥梁，并进行其自己的程序化一致的转化研究。 CIPT 的独特之处在于它集中了以下领域的经验：凭借分子生物学、基因组学、成像分析方面的专业知识开展早期临床试验，系统生物学、统计学和生物标志物开发。 CIPT 成员将科学发现转化为实验室和临床的新范例，并定位在这个多学科框架内获得高影响力转化研究所需的专业知识。高影响力的转化项目是优先获得机构支持。 CIPT有来自22个系和7个学院的60名成员。 CIPT 研究资金充足，每年获得 560 万美元的直接同行评审资助支持，其中 440 万美元用于癌症- 集中（9 个多 PI），来自 NCI 的 230 万美元（8 个 R01 等效/7 个 PI，1 个 UM1）。在上一个资助期内 CIPT 成员发表了 929 篇论文，其中 42% 是合作论文（29% 为内部合作论文，25% 为内部合作论文）合作），其中 51% 与其他机构合作。这表明总量和与上一个项目期间相比的合作出版物。有影响力的科学包括发现与癌症合作重新激活 p53 特定构象突变体的化合物药理学课程（CP）； MAPK通路与细胞凋亡合理结合的进展抑制，并通过与癌症合作抑制自噬来靶向癌症代谢新陈代谢和生长计划（CMG）；以及对 PARP 抑制剂耐药机制的鉴定与基因组不稳定性和癌症遗传学计划 (GICG) 合作研究 BRCA1 突变癌症。这些正在临床和小鼠模型中评估这些方法。 CIPT 调查人员与 CMG 合作并 GICG 研究人员将确定免疫检查点治疗反应的新标志物，包括存在子宫内膜癌中的 DNA 聚合酶-ε 突变。与 CP 领导的生物医学工程师合作开发分类器以帮助指导早期 ER+ 乳腺癌的治疗数字组织学图像的计算分析。与癌症防治的合作项目 (CPC) 开展了评估精神疾病对老年人乳腺癌结局影响的研究。最后，默克尔细胞癌免疫检查点疗法的临床研究导致 FDA 批准 avelumab 用于晚期疾病。 CIPT 科学由研究计划中的发现转化推动，并对临床发现进行反向翻译，以确定新的反应和耐药分子机制。 CPC，第 I 部分：叙述，第 1 页，共 1 页；草稿 2018 年 1 月 19 日 11:56