Screening for protein interaction inhibitors of the ERKS axis for brain tumor treatment
About This Grant
PROJECT SUMMARY Malignant brain tumors such as glioblastomas are among the most lethal cancers. The five-year survival estimates for glioblastoma are a dismal 4 to 5%, additional treatment options are thus urgently needed. In our studies on how proliferation and differentiation are regulated during normal brain development, we identified a protein-protein interaction network comprising EphrinB, RGS3, KIF20A and SEPT7, which sequentially binds to one another (referred to as the ERKS axis). Genetic functional results demonstrated that the ERKS axis proteins are essential for maintaining a proliferative state of normal neural progenitor cells and loss-of-function of the axis leads to differentiation. Because tumors often originated from progenitor/stem cells that lost the control on proliferation vs. differentiation decisions, we reasoned that the ERKS axis may act similarly in brain tumor progenitor/stem cells to control proliferation. In proof-of-concept studies, we depleted the mitotic kinesin KIF20A in cancerous progenitor/stem cells in animal models of brain tumors. Depletion promoted daughter cells to undergo a differentiative path, which blocked cell proliferation leading to suppression of brain tumor growth. In addition, disruption of protein-protein interaction (PPI) within the ERKS axis by competitive inhibition with protein binding domains could block the growth of brain tumor stem cells. These results thus indicate that the ERKS axis proteins can serve as targets for developing novel differentiation therapy for brain tumor treatment. In this study, we propose to develop inhibitors targeting specific interactions within the ERKS axis. We will employ a PPI- based high throughput screening (HTS) assay to isolate small molecule inhibitors from compound libraries and further validate candidate hits using additional secondary and tertiary cell free and cell-based protein binding assays as well as cellular functional assays. We anticipate that the proposed studies will identify and validate candidate hit inhibitors of the ERKS axis, providing a foundation for further developing the lead molecules into potential therapeutics for clinic use in brain tumor treatment.
Grant Summary
Screening for protein interaction inhibitors of the ERKS axis for brain tumor treatment is a NCI - National Cancer Institute grant providing up to $736K for university, nonprofit, healthcare org. Applications are due 2029-05-31 (open). Check eligibility and apply with FindGrants.
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Up to $736K
2029-05-31
- 1Confirm your organization is eligible for Screening for protein interaction inhibitors of the ERKS axis for brain tumor treatment 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.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
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Screening for protein interaction inhibitors of the ERKS axis for brain tumor treatment: Frequently Asked Questions
Who is eligible for the Screening for protein interaction inhibitors of the ERKS axis for brain tumor treatment?
Screening for protein interaction inhibitors of the ERKS axis for brain tumor treatment 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 Screening for protein interaction inhibitors of the ERKS axis for brain tumor treatment provide?
Screening for protein interaction inhibitors of the ERKS axis for brain tumor treatment provides up to $736K 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 Screening for protein interaction inhibitors of the ERKS axis for brain tumor treatment deadline?
Applications for Screening for protein interaction inhibitors of the ERKS axis for brain tumor treatment are due 2029-05-31 (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 Screening for protein interaction inhibitors of the ERKS axis for brain tumor treatment?
To apply for Screening for protein interaction inhibitors of the ERKS axis for brain tumor treatment, 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.