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Targeted therapy in ex vivo medulloblastoma/PNET

离体髓母细胞瘤/PNET 靶向治疗

基本信息

批准号：
7736806
负责人：
JAMES M OLSON
金额：
$ 22.34万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-12-06 至 2011-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7736806
关键词：
Apoptosis Apoptotic BMP2 gene Biological Biological Markers Biology Carboplatin Cell Death Cells Child Childhood Childhood Brain Neoplasm Children&apos s Oncology Group Cisplatin Clinical Data Clinical Trials Correlative Study Cytotoxic Chemotherapy Data Development Diagnosis Disease Drug Kinetics Etoposide Excision Failure Foundations Future Goals Growth Histone Deacetylase Inhibitor Hour Human Impaired cognition Inhibitory Concentration 50 Isotretinoin Laboratories Laboratory Finding Malignant - descriptor Malignant neoplasm of brain Modality Modeling Molecular Mus Operative Surgical Procedures Pathway interactions Patients Pharmaceutical Preparations Phase III Clinical Trials Predictive Value Primary Neoplasm Radiation Radiation therapy Radiation-Sensitizing Agents Radiosensitization Radiosurgery Randomized Relapse Research Personnel Resistance Retinoids Series Signal Pathway Specimen Supratentorial Survivors Testing Toxic effect Translating Tretinoin Work base chemotherapy cohort combinatorial cyclopamine drug distribution drug efficacy high risk inhibitor/antagonist innovation medulloblastoma medulloblastoma cell line molecular marker neoplastic cell notch protein outcome forecast pre-clinical prognostic prognostic indicator resistance mechanism response treatment strategy tumor tumor growth tumor xenograft

项目摘要

Children with medulloblastoma/PNET are currently treated with surgery, radiation, and chemotherapy. Survivors often suffer severe long-term toxicity from these treatments. Our laboratory has shown in ex vivo specimens from human medulloblastoma and mouse medulloblastoma models that targeted therapies including 13-cis retinoic acid (RA), cyclopamine, notch pathway inhibitors, histone deacetylase inhibitors and combinations of these agents induce medulloblastoma cell death as well as more toxic chemotherapy agents that are currently used for these patients. Based on our findings related to 13-cis RA, the Children's Oncology Group has developed a national Phase III clinical trial to assess efficacy of this agent. The broad long term goals of the biology correlative studies to this clinical trial are to 1) identify biomarkers with prognostic and predictive value for future clinical trials and 2) prioritize candidate targeted therapies for future clinical trials. The specific aims of this proposal are to utilize ex vivo surgical specimens to 1) identify biomarkers predicting therapy failure in high-risk medulloblastomas/SPNETs and 2) prioritize targeted therapies for future clinical trials. The significance of this work is that it is a direct means toward replacing current pediatric brain tumor treatment modalities with more effective and less toxic alternatives.

髓母细胞瘤/PNET患儿目前的治疗方法包括手术、放疗和化疗。