Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chip
About This Grant
ABSTRACT Lung metastasis is the primary cause of death in osteosarcoma (OSA) patients, with 5-year survival rates of approximately 20% using current treatments. Our recent findings highlight the need to target both tumor and microenvironment-derived factors, revealing that resident lung and immune cells released growth factors that activated tumor survival pathways upon metastasis, particularly prosurvival gene, MCL1. Inhibiting MCL1, especially when combined with cyclophosphamide, showed promising results in our preclinical model studies, eradicating metastatic lesions in some cases. However, several questions remain as to the specificity of MCL1 as a target and the feasibility of targeting this prosurvival pathway for osteosarcoma treatment. To this end, in Aim 1, we will deploy a novel bioengineered bone and lung model for real-time cell tracking to definitively establish the role of MCL1 in lung metastasis and validate these findings in vivo. We will then identify MCL1 inhibitors most able to eliminate metastases in our engineered model, in vivo, and test their safety in preclinical models. In Aim 2, we will identify mechanisms linking microenvironment-driven osteosarcoma signaling and MCL1 regulation in the lung. By using ex vivo and in vivo approaches, we will pinpoint critical ligand-receptor interactions and test receptor-level inhibitors, aimed at blocking the effects, to reduce metastatic osteosarcoma MCL1 protein levels. Promising inhibitors will then be evaluated for their effectiveness in combination with low- dose MCL1 inhibitors to eliminate lung metastasis and safety in preclinical models. Overall, this proposal aims to fully validate the potential of MCL1 inhibitors and explore combinatorial therapies to enhance efficacy and reduce toxicity, using innovative tumor-host interaction models, paving the way for future clinical trials.
Grant Summary
Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chip is a NCI - National Cancer Institute grant providing up to $625K for university, nonprofit, healthcare org. Applications are due 2031-02-28 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $625K
2031-02-28
- 1Confirm your organization is eligible for Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chip 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.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NCI - National Cancer Institute before the deadline.
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Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chip: Frequently Asked Questions
Who is eligible for the Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chip?
Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chip 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 Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chip provide?
Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chip provides up to $625K 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 Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chip deadline?
Applications for Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chip are due 2031-02-28 (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 Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chip?
To apply for Direct and indirect MCL1 targeting for high-efficiency therapy of lung metastasis in-vivo and on-a-chip, 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.