Development of miRNA-based approach for pediatric high-grade gliomas
About This Grant
ABSTRACT Primary high-grade gliomas (pHGGs) constitute the leading cause of cancer-related mortality in children and adolescents aged. Initial treatment strategies typically consist of gross total resection, when feasible, followed by focal radiotherapy and chemotherapy. However, the choice/use of chemotherapy remains uncertain. Although numerous therapeutic approaches have been tested, outcomes remain dismal. Since there is no standard chemotherapy for pHGGs, new treatments are urgently needed. To overcome the clinical challenges related to developing new treatments for pHGGs, our primary objective for this project is to develop a new tumor-targeting therapeutic agent that is specifically designed for pHGGs on a molecular basis. Recent studies revealed significant differences in the miRNA expression profiles between pHGGs and normal brain tissues, indicating that several sets of miRNA are oncogenic and highly overexpressed in pHGGs. Specifically, our preliminary data showed that miR20a is aberrantly expressed and has an oncogenic function in pHGGs including glioblastomas (pGBM) and diffuse intrinsic pontine glioma (DIPG, diffuse midline glioma). Although pGBM and DIPG are pathologically different types of highly lethal pHGGs, they share oncogenic molecular profiles, suggesting that we can attack the same molecular targets for both pGBM and DIPG. Given that aiming to diminish oncogenic miRNA expression by using antisense-miRNA is a promising strategy, delivery of antisense-miRNA is currently the major challenge [e.g., lack of tumor targeting, poor transport, and cellular penetration]. To overcome these challenges, we developed a cell-penetrating peptide (p28)-conjugated with antisense-miR20a (namely AmiR20-p28). Our preliminary results showed that systemically injected AmiR20-p28 preferentially accumulates at the tumor lesion in the brain, and induces apoptotic cell death by significantly silencing endogenous miR20a in tumors and blood (circulating miR20a as a potential biomarker), thereby extensively prolonging the survival of mice bearing pGBM. Based on our data, we hypothesize that the development of a pHGG tumor-targeting AmiR20-p28 will provide a novel therapeutic tool. To test our hypothesis, we set realistic aims; Aim1) Determine the pharmacological activities of AmiR20- p28 in pHGGs. Aim2) Establish biomarkers, pharmacokinetics, and toxicity of AmiR20-p28. Our experimental plans were designed with multiple validations and blinded conditions, and our multi-disciplinary team integrates expertise in basic, translational, and clinical brain cancer biology, molecular biology, pathology, and biostatistics. We seek to overcome current limitations by using AmiR20-p28 for pHGGs for which there is no cure. Upon completing our aims, our unique approach can provide a broad impact on developing CPP/miRNA- based agents for pHGGs. It can also potentially provide better treatment strategies for pHGGs patients, which is a major milestone and relevant to the NIH focus area.
Grant Summary
Development of miRNA-based approach for pediatric high-grade gliomas is a NCI - National Cancer Institute grant providing up to $545K for university, nonprofit, healthcare org. Applications are due 2031-03-31 (open). Check eligibility and apply with FindGrants.
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Up to $545K
2031-03-31
- 1Confirm your organization is eligible for Development of miRNA-based approach for pediatric high-grade gliomas from NCI - National Cancer Institute, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
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Development of miRNA-based approach for pediatric high-grade gliomas: Frequently Asked Questions
Who is eligible for the Development of miRNA-based approach for pediatric high-grade gliomas?
Development of miRNA-based approach for pediatric high-grade gliomas is offered by NCI - National Cancer Institute and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Development of miRNA-based approach for pediatric high-grade gliomas provide?
Development of miRNA-based approach for pediatric high-grade gliomas provides up to $545K per award from NCI - National Cancer Institute. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Development of miRNA-based approach for pediatric high-grade gliomas deadline?
Applications for Development of miRNA-based approach for pediatric high-grade gliomas are due 2031-03-31 (open). Because deadlines can change, verify the date with the funder, NCI - National Cancer Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Development of miRNA-based approach for pediatric high-grade gliomas?
To apply for Development of miRNA-based approach for pediatric high-grade gliomas, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NCI - National Cancer Institute.