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CROC

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Unravelling ChemoResistance mechanisms and improving first-line therapeutic stra...

Unravelling ChemoResistance mechanisms and improving first-line therapeutic strategies in high-grade serous Ovarian Carcinoma using multi-culture patient-derived organoids To improve the poor clinical outcomes in high-grade serous ovarian carcinoma (HGSC), we need to understand the cancer cell-tumour microenvironment (TME) dynamic interactions upon disease evolution and treatment. In my proposed pro... ver más

31/12/2024

UCPH

215K€

Presupuesto del proyecto: 215K€

Líder del proyecto

KOBENHAVNS UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

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Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-06-13

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

HORIZON-MSCA-2021-PF-01-01: MSCA Postdoctoral Fellowships 2021

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1 Participantes

UCPH

214.93K€ | Lider

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Duración del proyecto: 30 meses Fecha Inicio: 2022-06-13
Fecha Fin: 2024-12-31

Líder del proyecto

KOBENHAVNS UNIVERSITET

TRL 4-5

Presupuesto del proyecto 215K€

Descripción del proyecto To improve the poor clinical outcomes in high-grade serous ovarian carcinoma (HGSC), we need to understand the cancer cell-tumour microenvironment (TME) dynamic interactions upon disease evolution and treatment. In my proposed project, I will establish a unique TME-HGSC patient-derived organoid (PDO) multi-culture model system to identify and understand how the TME impacts treatment responses and how treatment resistance can be overcome. To generate multi-culture PDO preclinical models of HGSC for the first time, I will use my own expertise in 3D culture and stromal cell isolation from patient-derived material, and I will integrate self-generated TME units with well-characterized HGSC PDOs established at the host laboratory. I will then use this model to study the chemotherapy-induced changes at the single cell level. I will compare the transcriptional states of the treated models to the interval/recurrent PDOs and correlate their in vitro treatment responses to the patient responses. I will predict strategies to increase the sensitivity of the cancer cells to the HGSC standard treatment by targeting the tumour-TME interactions or the cancer cells themselves without generating a more tumour-supportive TME, by using the multi-culture PDOs in high-throughput drug screens and subsequently integrating the generated data. Finally, I will functionally validate the predicted therapeutic strategies by CRISPR gene editing and drug treatment of the models. I expect that my project will generate profound knowledge on the chemoresistance mechanisms in HGSC and provide the scientific community with a unique experimental model that incorporates the TME to state-of-the-art HGSC PDOs. In addition, this fellowship will allow me to enhance my international visibility through high-impact publications independent from my PhD supervisor and provide me with a great track record in obtaining independent funding, essential to successfully secure independent research grants in the future.

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