PDX-PC · Elucidation of tumour cell plasticity mechanisms associated to treatment in metastatic prostate cancer
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2019-09-16 → 2021-09-15
- Финансиране от ЕС
- 166 203 €
- Участници
- 2
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Молекулярните механизми, чрез които клетките при метастатичен рак на простатата променят свойствата си под влияние на лечението, се анализират чрез модели от пациентски тъкани. Разбирането на тези процеси помага за определяне на по-ефективни последователности от терапии при напреднали стадии на болестта.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Elucidation of tumour cell plasticity mechanisms associated to treatment in metastatic prostate cancer
Prostate cancer (PC) is the second most commonly diagnosed malignancy in the world and the fifth leading cause of cancer mortality in men. In patients with earlier stages the disease can be mild and curable but unfortunately, when it spreads throughout the body it ends in a fatal outcome. PC is a highly heterogeneous disease. This means that despite the wide spectrum of drugs available nowadays, not all patients respond to these treatments in the same manner. Furthermore, PC is plastic, which implies that not only time but also the administration of some treatments are responsible for generating molecular changes that limit the effectiveness of the subsequent therapies. This is why understanding the altered biological pathways behind such plasticity processes is crucial and would contribute to establishing optimal sequential treatment strategies that might result in better overall clinical outcomes at advanced stages of the disease. This project aims to elucidate the molecular mechanisms responsible for tumour cell plasticity associated with treatment in metastatic PC by using patient-derived xenografts (PDX) in vivo models. In contrast to other pre-clinical models in PC, PDX preserve the molecular heterogeneity and therapeutic responses observed in clinical settings, thus providing a close-to-reality approach to address the goals of this project.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Prostate cancer (PC) is among the top five leading malignancies causing cancer mortality worldwide. Increased prevalence and declined mortality rate have led to an increment in follow-ups with a significant rise in the economic burden. In the last few years, several new options for metastatic disease have been approved leading to clinicians to have multiple choices of therapy sequences. However, not all patients initially respond and most of them eventually develop resistance. The ability of tumour cells to reprogram themselves and survive despite the blocked targets (tumour cell plasticity) may accounts for the absence of durable responses. In addition, the fact that initial treatments may affect the potential benefit of subsequent treatments highlights the need to discover predictive biomarkers for optimal treatment selection, allowing early changes in treatment for non-responding patients. This multidisciplinary project aims to elucidate the molecular mechanisms responsible for tumour cell plasticity associated to treatment response in metastatic PC. Patient-derived xenografts (PDX) in vivo models will be used, since they preserve molecular heterogeneity and therapeutic response observed in the clinic. They will be treated under different regimens. Tumour tissues will be analysed by RNA sequencing before and after treatment. Bioinformatics analysis will be used to establish molecular signatures of treatment response that will be validated in liquid biopsy (circulating tumour cells and cell free DNA) from metastatic PC patients undergoing different treatments. PDX-PC will provide a better understanding of the molecular evolution of the disease that will contribute to design more specific and individualized treatments. In the setting of non-curative therapy, the implementation of such molecular findings at clinical practice may help to guide treatment decisions, improve outcomes, and prevent unnecessary side effects and costly therapies in men with metastatic PC.
Оригинален текст от CORDIS (на английски).
Участници
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Данни: CORDIS, © Европейски съюз