HEИндивидуална стипендия2023–2025

CROC · Unravelling ChemoResistance mechanisms and improving first-line therapeutic strategies in high-grade serous Ovarian Carcinoma using multi-culture patient-derived organoids

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2023-01-01 → 2025-08-31
Финансиране от ЕС: 239 492 €
Участници: 1
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Механизмите на устойчивост към химиотерапия при рак на яйчниците се изучават чрез нови модели от пациентски клетки. Това помага за разбирането на процесите, при които туморът оцелява, за да се подобрят стратегиите за лечение.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Unravelling ChemoResistance mechanisms and improving first-line therapeutic strategies in high-grade serous Ovarian Carcinoma using multi-culture patient-derived organoids

Ovarian cancer is the deadliest cancer of the female reproductive system. Even after undergoing surgery and anti-cancer therapy, most women recur in less than 3 years and eventually show resistance to the treatment. To develop better treatments for these women, we need to investigate and understand how treatment resistance occurs at the cellular level. And to conduct such investigations, the development of research models that better mimic the tumors from the patients is crucial. Since tumors are not comprised of isolated cancer cells but these are rather in constant communication with other cell types (stromal cells), my first goal was to create a new research model incorporating both cancer cells (grown as stable organoids) and stromal cells from ovarian cancer patients. When this project started, such research model did not exist. My second goal was to identify the cellular mechanisms of resistance to anti-cancer therapy in ovarian cancer patients and to design new treatments. To do so, I used a technique called single cell RNA sequencing and studied the changes that occur in the cancer cells and the stromal cells of my research models when they are exposed to the anti-cancer therapy given to patients. With this information, I found cellular processes that are unique to the cancer cells that survive the anti-cancer therapy and that are regulated by the stromal cells, and I investigated if such processes could be blocked with additional treatments.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

KOBENHAVNS UNIVERSITET · KOBENHAVNКоординаторДания