Diversity Supplement to Targeted Therapy in Ex Vivo Medulloblastoma/PNET
体外髓母细胞瘤/PNET 靶向治疗的多样性补充
基本信息
- 批准号:10380520
- 负责人:
- 金额:$ 6.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2021-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAlternative TherapiesAmendmentAppearanceBiologicalCell LineCellsChildChildhood Brain NeoplasmClinicalClinical DataClinical TrialsDataDiseaseDoseEpendymomaExposure toFDA approvedFundingFutureGene ExpressionGenomicsGliomaGrantHeterogeneityHistopathologyHumanLeadMYCN geneMediatingPathway interactionsPatientsPediatric Oncology GroupPharmaceutical PreparationsPhase III Clinical TrialsPhenotypePrimitive Neuroectodermal TumorPrognosisPrognostic MarkerRadiationRadiation exposureResearchRhabdoid TumorSpecimenSupratentorialSupratentorial NeoplasmsTissuesWorkXenograft ModelXenograft procedureantibody engineeringcancer cellcell killingdrug candidateefficacy studyfunctional genomicsgenome wide methylationhigh riskhigh risk populationin vivoirradiationmacrophagemedulloblastomamouse modelparticipant enrollmentpre-clinicalradiation resistanceradioresistanttargeted treatment
项目摘要
PROJECT SUMMARY/ABSTRACT
I lead the Children’s Oncology Group Phase III clinical trial, ACNS0332, which evaluates treatment options for
children with high-risk medulloblastoma (the most common pediatric brain tumor) and supratentorial primitive
neuroectodermal tumors (sPNETs). The study opened in 2007 and underwent a major amendment in 2014,
when emerging data revealed biological disparity between medulloblastomas and sPNETs, as well as
heterogeneity in sPNET patients. We discontinued sPNET patient enrollment when genomic analyses funded
by the prior cycle of this grant revealed that 71% of the non-pineal sPNET patients were actually high grade
glioma, ependymoma, or atypical teratoid rhabdoid tumors, despite sPNET appearance by histopathology. This
reveals the limitations of traditional histopathology and shows that contemporary genomic analyses could
spare many children from receiving craniospinal irradiation that is not necessary and not helpful.
In Aim 1 of this renewal application, we extend the genomic studies to the 300 medulloblastoma patients in the
study. We collected research tissue from more than 95% of these patients and anticipate that the studies will
reveal: 1) patient groups who are likely to die from their disease despite the intense therapy on ACNS0332;
and 2) patient groups who were placed on ACNS0332 because of clinical or histopathologic observations and
who may include a mixture of good prognosis patients (e.g., those who would fare well with much less radiation
than provided on ACNS0332), as well as patients with genomically-predicted poor prognosis, who should be
stratified differently in the future.
In Aim 2 we address the radiation resistance phenotype of the worst prognosis patients, particularly those with
amplified MYC or MYCN. We will collect pre- and post-radiation specimens from patient-derived orthotopic
xenograft (PDOX) models (14 MYC/MYCN amplified) that we generated and characterized in the prior cycle of
this grant, other PDOX models that we receive from four collaborators, and matching cell lines that we
generated and characterized. We will use the cell lines to screen FDA approved drugs for those that overcome
radiation resistance and to conduct functional genomic screens to identify pathways that, when inhibited,
convert radiation resistant cells into radiation sensitive cells. In vivo efficacy studies on PDOX mouse models
representing dozens of patients will follow.
In the Diversity Supplement, we remain focused on MYC/MYCN-amplified medulloblastoma and use the
same PDOX lines to assess whether a multispecific antibody that we engineered to overcome radiation
resistance is sufficient to induce macrophage-mediated cancer cell killing when locally administered.
The significance is that this work will likely reduce unnecessary radiation exposure to patients who do not
warrant high-dose craniospinal irradiation, identify patients who would best be served by alternative therapies,
and generate pre-clinical data to prioritize the most effective agents for upcoming human clinical trials.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JAMES M OLSON其他文献
JAMES M OLSON的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JAMES M OLSON', 18)}}的其他基金
Engineering Knotted Peptide Therapeutics for Pediatric Brain Tumor Patients
针对小儿脑肿瘤患者的工程打结肽治疗
- 批准号:
10531428 - 财政年份:2022
- 资助金额:
$ 6.99万 - 项目类别:
Engineering knotted peptide therapeutics for pediatric brain tumor patients
为儿童脑肿瘤患者设计打结肽疗法
- 批准号:
9897193 - 财政年份:2019
- 资助金额:
$ 6.99万 - 项目类别:
Combinations of Synergistic Bispecific Human Antibodies: A Novel Strategy for the Treatment of Neuroblastoma
协同双特异性人类抗体的组合:治疗神经母细胞瘤的新策略
- 批准号:
10228852 - 财政年份:2018
- 资助金额:
$ 6.99万 - 项目类别:
Engineering knotted peptide therapeutics for pediatric brain tumor patients
为儿童脑肿瘤患者设计打结肽疗法
- 批准号:
10083110 - 财政年份:2018
- 资助金额:
$ 6.99万 - 项目类别:
Sideport Needle Array Technologies for Prioritizing Drugs for Cancer Patients
用于优先考虑癌症患者药物的侧端口针阵列技术
- 批准号:
8294620 - 财政年份:2011
- 资助金额:
$ 6.99万 - 项目类别:
相似海外基金
Development of education and dissemination methods for psychiatric nurses to introduce complementary and alternative therapies from the physical side
开发精神科护士的教育和传播方法,从身体方面引入补充和替代疗法
- 批准号:
26463484 - 财政年份:2014
- 资助金额:
$ 6.99万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Alternative therapies for antibiotic-resistant Helicobacter pylori infection
抗生素耐药性幽门螺杆菌感染的替代疗法
- 批准号:
23590890 - 财政年份:2011
- 资助金额:
$ 6.99万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Alternative Therapies for Benign Prostate Symptoms
良性前列腺症状的替代疗法
- 批准号:
8147503 - 财政年份:2010
- 资助金额:
$ 6.99万 - 项目类别:
Scientific evaluation of therapeutic effects and mechanism of alternative therapies using PET molecular imaging technique.
利用PET分子成像技术科学评估替代疗法的治疗效果和机制。
- 批准号:
21590754 - 财政年份:2009
- 资助金额:
$ 6.99万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Treating Burn injuries: First-aid and alternative therapies
治疗烧伤:急救和替代疗法
- 批准号:
nhmrc : 409902 - 财政年份:2006
- 资助金额:
$ 6.99万 - 项目类别:
NHMRC Postgraduate Scholarships
PREVENTING COGNITIVE DECLINE WITH ALTERNATIVE THERAPIES
通过替代疗法预防认知能力下降
- 批准号:
7206559 - 财政年份:2005
- 资助金额:
$ 6.99万 - 项目类别: