MDACC-PREDICT

MDACC-预测

• 批准号: 10253153
• 负责人: Scott Kopetz
• 金额: $ 66.99万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10253153
• 关键词: Acetates; Affect; Algorithms; Biological; Biological Assay; Biological Factors; Biological Markers; Biological Process; Biopsy; Cancer Etiology; Cancer Model; Cancer Patient; Cessation of life; Cetuximab; Characteristics; Chronobiology; Clinical; Clinical Trials; Colorectal Cancer; Community Clinical Oncology Program; Coupled; DNA; Data; Data Analyses; Development; Diet; Epidermal Growth Factor Receptor; Gene Expression Profile; Genomic approach; Glutaminase; Glutamine; Histologic; Human; Image; Imaging Device; Individual; Knowledge; Lead; Ligands; Location; MAP Kinase Gene; Malignant Neoplasms; Measures; Mediating; Metabolism; Methods; Molecular; Molecular Genetics; Monoclonal Antibodies; Monoclonal Antibody Therapy; Mus; Nature; Oncology; Outcome; Patients; Phase I/II Clinical Trial; Phenotype; Positron-Emission Tomography; Protocols documentation; RNA; Radiochemistry; Receptor Inhibition; Refractory; Regimen; Reproducibility; Research; Resistance; Resources; Standardization; TP53 gene; Technology; Therapeutic; Tracer; Universities; University of Texas M D Anderson Cancer Center; Validation; Vision; Xenograft Model; Xenograft procedure; attenuation; base; circadian; clinical imaging; colon cancer patients; experience; genomic data; genomic predictors; imaging modality; improved; inhibitor/antagonist; irinotecan; mouse model; neutralizing monoclonal antibodies; novel; panitumumab; personalized cancer therapy; pre-clinical; precision oncology; preclinical imaging; preclinical study; predicting response; quantitative imaging; reconstruction; response; subcutaneous; targeted treatment; tool; treatment optimization; tumor

Project Summary This application proposes a new U24 Oncology Co-Clinical Imaging Resource entitled VU-PREDICT (Vanderbilt University-PET imaging Resource to Enhance Delivery of Individualized Cancer Therapeutics). Precision cancer medicine, which seeks to exploit unique cellular, molecular and genetic characteristics of individual tumors to optimize treatment, remains a critically unmet need. Despite advances in biomarker technologies that yield high-quality cellular and genomic data, critical gaps remain to consistently match patients with cancer and ideal therapies. While `predictive' genomic assays based on RNA and DNA are now commonplace, current methods largely ignore tumor phenotypes differentiable by quantitative imaging. The overarching vision for VU-PREDICT is a suite of quantitative imaging tools that facilitate the discovery of novel, predictive imaging-derived gene expression signatures; such signatures can be deployed by the greater oncology community to improve the personalization of cancer treatment. The linchpin of VU-PREDICT will be positron emission tomography (PET) imaging. The sensitive and quantitative nature of PET, coupled with the ability to produce biologically active PET tracers, renders PET uniquely capable of both detecting tumors and profiling their specific features. Complementary to genomic approaches, PET imaging provides a quantitative, functional measure of tumor phenotype, and when coupled biopsy approaches, can provide a significantly greater breadth of biological characterization. VU-PREDICT centers on a parallel co-clinical trial of patients with advanced colorectal cancer (CRC) and human-in-mouse PDX (patient-derived xenograft) models. CRC is a leading cause of cancer-related deaths worldwide. Epidermal growth factor receptor (EGFR) neutralizing monoclonal antibodies (mAbs; cetuximab, panitumumab) are approved for treatment of advanced wild-type (WT) RAS CRC. However, durable responses to anti-EGFR mAbs occur in only 12–17% of patients. VU-PREDICT will capitalize upon a Phase I/II clinical trial opening at Vanderbilt combining a glutaminase (GLS1) inhibitor (CB-839, Calithera), EGFR mAb therapy (panitumumab) and irinotecan in patients with advanced and refractory WT RAS CRC. It is anticipated that combining CB-839 with EGFR mAb therapy will resensitize refractory CRC patients with Gln- avid tumors to EGFR blockade. VU-PREDICT will allow our development of quantitative PET imaging measures within this trial and in related preclinical studies that may identify patients likely to respond to combined GLS1/EGFR inhibition. We have four Specific Aims: (1) Optimize quantitative preclinical PET imaging protocols for Gln metabolism; Implement quantitative 18F-FSPG PET (2), 11C-Acetate PET (3), and dual-tracer 11C-Acetate/18F-FSPG PET (4) to discover predictive, imaging-derived gene expression signatures.

项目概要 本申请提出了一个新的 U24 肿瘤联合临床影像资源，名为 VU-PREDICT （范德比尔特大学-PET 成像资源，以增强个体化癌症治疗的实施）。 精准癌症医学，旨在利用癌症独特的细胞、分子和遗传特征 个体肿瘤以优化治疗，仍然是一个严重未满足的需求。尽管生物标志物取得了进步 产生高质量细胞和基因组数据的技术，仍然存在关键差距 癌症患者和理想的治疗方法。虽然基于 RNA 和 DNA 的“预测”基因组检测现在已 常见的是，当前的方法很大程度上忽略了可通过定量成像区分的肿瘤表型。这 VU-PREDICT 的总体愿景是一套定量成像工具，有助于发现新颖的、 预测成像衍生的基因表达特征；这样的签名可以由更大的人部署 肿瘤学界致力于提高癌症治疗的个性化。 VU-PREDICT 的关键将是 正电子发射断层扫描（PET）成像。 PET 的灵敏性和定量性，加上 能够产生生物活性 PET 示踪剂，使 PET 具有独特的能力，能够检测肿瘤和 分析他们的具体特征。作为基因组方法的补充，PET 成像提供了定量、 肿瘤表型的功能测量，以及联合活检方法，可以提供显着的结果 更广泛的生物学特征。 VU-PREDICT 重点关注晚期结直肠癌 (CRC) 患者的平行联合临床试验 和人鼠 PDX（患者来源的异种移植）模型。 CRC 是癌症相关疾病的主要原因 全世界的死亡人数。表皮生长因子受体 (EGFR) 中和单克隆抗体 (mAbs； 西妥昔单抗、帕尼单抗）被批准用于治疗晚期野生型 (WT) RAS CRC。然而， 只有 12-17% 的患者对抗 EGFR mAb 产生持久反应。 VU-PREDICT 将利用 范德比尔特大学启动结合谷氨酰胺酶 (GLS1) 抑制剂（CB-839，Calithera）的 I/II 期临床试验， EGFR 单克隆抗体疗法（帕尼单抗）和伊立替康治疗晚期难治性 WT RAS CRC 患者。这是 预计 CB-839 与 EGFR mAb 疗法相结合将使难治性 CRC 患者对 Gln- 重新敏感 肿瘤对 EGFR 阻断有强烈的需求。 VU-PREDICT 将帮助我们开发定量 PET 成像 本试验和相关临床前研究中的措施可能会确定可能对以下药物产生反应的患者 联合 GLS1/EGFR 抑制。我们有四个具体目标： (1) 优化定量临床前 PET Gln 代谢成像方案；实施定量 18F-FSPG PET (2)、11C-Acetate PET (3) 和 双示踪剂 11C-Acetate/18F-FSPG PET (4) 用于发现预测性、成像衍生的基因表达特征。