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Metabolic mechanisms underpinning obesity-driven pancreatic cancer

Project description

Investigating the metabolic link between obesity and pancreatic cancer

Pancreatic cancer is a lethal malignancy with a high rate of metastatic spread and poor prognosis; therefore, the need to find new therapies is urgent. Pancreatic tumours contain an extremely high proportion of normal cells that become part of the tumour mass and contribute to malignant progression, and obesity is strongly associated with the development of the disease. The EU-funded PancObese project aims to understand the mechanisms underlying the relationship between obesity and pancreatic cancer, investigating the metabolic link between the tumour cells and adipocytes in the tumour environment. Metabolomic analyses and in vivo models will be used to identify novel mechanisms that underpin pancreatic cancer progression, providing a rationale for the development of new therapeutic options.

Objective

Pancreatic cancer is one of the most lethal malignancies, showing a high rate of metastatic spread and a dismal prognosis. With almost no effective treatment options, new therapies to treat this devastating disease are urgently needed. Such advances will depend on a better understanding of the mechanisms that drive pancreas cancer progression. Previous work has revealed two interesting features of pancreas cancer on which this proposal is built. Firstly, pancreas cancers contain an extremely high stromal component – normal cells that become part of the tumour mass and contribute to the control of malignant progression. Secondly, obesity – a rapidly growing epidemic worldwide – is associated with increased pancreas cancer development. This proposal aims to understand the mechanisms underlying the link between obesity and pancreas cancer, focusing on the metabolic cross talk between the adipocytes in the tumour environment and the tumour cells themselves. This is a pioneering project that pulls together critical aspects of pancreas cancer biology, building on a solid platform of existing knowledge around the importance of metabolic alterations in cancer and the role of other types of tumour associated stromal cells. State of the art metabolomic analyses and in vivo models will be used to identify novel aspects of metabolic control of the tumour cell environment, how these changes promote pancreas cancer progression and the impact of obesity on these responses. Focusing on the importance of adipocytes, the modulation of reactive oxygen species and the metabolite formate, we will apply our extensive expertise to a new area of study, determining novel mechanisms that underpin pancreas cancer progression. Ultimately, the insights developed by this proposal will provide a rational basis for the development of new therapeutic options. These studies will therefore have far-reaching impact on one of the world’s most devastating diseases.

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Topic(s)

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Funding Scheme

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ERC-ADG - Advanced Grant

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Call for proposal

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(opens in new window) ERC-2020-ADG

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Host institution

THE FRANCIS CRICK INSTITUTE LIMITED
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.

€ 2 500 000,00
Address
1 MIDLAND ROAD
NW1 1AT London
United Kingdom

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Region
London Inner London — West Camden and City of London
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.

€ 2 500 000,00

Beneficiaries (1)

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