Predictive Markers to Personalize Medicine for Malignant Glioma

恶性胶质瘤个性化医疗的预测标记

• 批准号: 8918452
• 负责人: KENNETH D ALDAPE
• 金额: $ 24.25万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8918452
• 关键词: Adoption; Amendment; Angiogenesis Inhibitors; Antibodies; Biological Assay; Biological Markers; Blood; Brain; CTLA4 gene; Cancer Center; Classification; Clinical; Clinical Trials; Complex; CpG Island Methylator Phenotype; CpG Islands; Cytotoxic Chemotherapy; Detection; Development; Diagnostic; Diagnostic tests; Dideoxy Chain Termination DNA Sequencing; Discrimination; Disease; Doctor of Medicine; Ensure; Environment; Epigenetic Process; Formalin; Funding; Gene Expression; Gene Expression Profile; Genes; Genetic; Genomics; Glioma; Heterogeneity; Knowledge; Laboratories; MGMT gene; Malignant Glioma; Malignant neoplasm of brain; Messenger RNA; Methodology; Methylation; Molecular; Molecular Analysis; Mutation; New Agents; Outcome; Paraffin Embedding; Pathologic; Patient Selection; Patients; Phase; Phase II/III Trial; Phenotype; Prognostic Factor; Prognostic Marker; Radiation Therapy Oncology Group; Risk; Stratification Factors; System; Time; Tissue Banks; Tissues; Translating; Tumor Biology; Tumor Tissue; Validation; Work; angiogenesis; antiangiogenesis therapy; base; bevacizumab; bisulfite; chemoradiation; disease natural history; experience; genome-wide; immunoregulation; improved; innovation; mRNA Expression; molecular marker; neuropathology; novel; outcome forecast; personalized medicine; phase III trial; predictive marker; prognostic; promoter; prospective; randomized trial; response; success; targeted treatment; temozolomide; transcriptome sequencing; treatment response; treatment strategy; tumor

There is a gap in in the availability of predictive biomarkers that are necessary to personalize treatment for patients with GBM. A challenge has been to separate prognostic makers (those that predict the natural history of the disease) from predictive (those that predict response to a particular treatment). l/Vfe hypothesize that effective biomarkers of treatment response must be decoupled from prognostic influences. Furthermore, to maximize clinical utility, these biomarkers must be developed as high-throughput, validated diagnostics applicable to small quantities of formalin-fixed, paraffin-embedded (FFPE) tissue. The specific aims of Project 3 are: 1) Develop a novel clinical diagnostic to classify patients suitable for FFPE tissue and incorporating the most robust molecular prognostic markers. 2) Develop a predictive marker of response to anti-angiogenic therapy. 3) Develop a predictive marker of response to immunomodulation. In the initial MDACC Brain SPORE funding, we developed a 9-gene FFPE biomarker that distinguished favorable from unfavorable patient prognosis. The assay was validated, commercialized, and incorporated as a prospective stratification factor in a phase III trial evaluating the anti-angiogenesis inhibitor bevacizumab [Radiation Therapy Oncology Group (RTOG) 0825]. To further improve survival discrimination, we expanded the 9-gene signature to a more robust 19-gene. In addition, we identified an additional epigenetic prognostic signature, the glioma CpG-island methlylator phenotype (G-CIMP). Using >300 cases from M.D. Anderson Cancer Center (MDACC) we developed a unified four risk group system called the molecular-clinical, prognosticator (MCP) that combines clinicopathologic factors with gene expression, genetic, and epigenetic factors. The analytic approach in constructing the MCP and its improved prognostic classification will allow us to better develop predictive makers independent of prognostic influences. Based on our success in the initial SPORE funding period and leveraging our expertise in biomarker development and our close involvement with the RTOG we know propose renewal of this project.

在个性化治疗所必需的预测性生物标志物的可用性方面存在差距