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Elucidation of tumour cell plasticity mechanisms associated to treatment in metastatic prostate cancer

Project description

Predictive biomarkers in the treatment of metastatic prostate cancer

Prostate cancer (PC) is among the top five deadliest cancers worldwide. In recent years, several new options for the treatment of metastatic PC have been approved, providing additional therapeutic choices. However, not all patients respond to the treatments, and most of them eventually develop resistance. There is an urgent need for predictive biomarkers to assist in optimal treatment selection, allowing timely changes in the treatment of non-responding patients. The EU-funded PDX-PC project aims to elucidate the molecular mechanisms responsible for tumour cell plasticity associated with treatment response in cases of metastatic PC. Researchers will employ patient-derived xenografts as in vivo models and genomics analysis to understand the molecular evolution of the disease, which will allow them to design more specific and individualised treatments in the future.

Objective

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.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2018

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Coordinator

FUNDACIO DE RECERCA CLINIC BARCELONA-INSTITUT D INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 166 202,88
Address
CARRER ROSSELLO 149
08036 BARCELONA
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 166 202,88

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