Deciphering the mechanisms of resistance to anti-TROP2 cancer therapy using novel humanized mouse models
About This Grant
SUMMARY Anti-TROP2 antibody-drug conjugates are a new class of cancer drugs that have shown marked efficacy in treating aggressive cancers. One of these drugs, sacituzumab govitecan (SG), has been approved for treating advanced triple-negative breast cancer and hormone receptor-positive breast cancer. However, drug resistance significantly limits the rate of response to SG and the duration of the response. Identifying the resistance mechanism and developing counteracting strategies will have a significant impact on improving patient survival. However, the preclinical study of anti-TROP2 resistance mechanisms is impeded by the fact that all current human anti-TROP2 drugs do not recognize mouse TROP2 protein, and no spontaneous tumor models in immunocompetent hosts is available for anti-TROP2 studies. To overcome these barriers, we have generated a novel humanized TROP2 mouse model and generated spontaneous triple-negative breast cancer (TNBC) tumors in this model. We discovered that these tumors have heterogenous responses to anti-TROP2 ADC (SG). While some tumors showed remarkable responses to the treatment, others were completely refractory. We have established a unique collection of tumors and organoid lines that are either responsive or refractory to SG. These tumor models allow us for the first time to investigate the action of anti-TROP2 drugs in spontaneous tumors in immunocompetent preclinical models. Using these unique reagents, we will investigate the involvement of both cell-intrinsic and extrinsic mechanisms in anti-TROP2 drug resistance. These insights will open new avenues for future in-depth mechanistic investigations and developing strategies for improving response to anti-TROP2 cancer treatment.
Grant Summary
Deciphering the mechanisms of resistance to anti-TROP2 cancer therapy using novel humanized mouse models is a NCI - National Cancer Institute grant providing up to $432K for university, nonprofit, healthcare org. Applications are due 2028-03-31 (open). Check eligibility and apply with FindGrants.
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Up to $432K
2028-03-31
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Deciphering the mechanisms of resistance to anti-TROP2 cancer therapy using novel humanized mouse models: Frequently Asked Questions
Who is eligible for the Deciphering the mechanisms of resistance to anti-TROP2 cancer therapy using novel humanized mouse models?
Deciphering the mechanisms of resistance to anti-TROP2 cancer therapy using novel humanized mouse models 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 Deciphering the mechanisms of resistance to anti-TROP2 cancer therapy using novel humanized mouse models provide?
Deciphering the mechanisms of resistance to anti-TROP2 cancer therapy using novel humanized mouse models provides up to $432K 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 Deciphering the mechanisms of resistance to anti-TROP2 cancer therapy using novel humanized mouse models deadline?
Applications for Deciphering the mechanisms of resistance to anti-TROP2 cancer therapy using novel humanized mouse models are due 2028-03-31 (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 Deciphering the mechanisms of resistance to anti-TROP2 cancer therapy using novel humanized mouse models?
To apply for Deciphering the mechanisms of resistance to anti-TROP2 cancer therapy using novel humanized mouse models, 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.