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Exploiting vulnerabilities in protein synthesis for cancer diagnosis and therapy

Objective

Tumor growth requires continuous synthesis of proteins, nucleic acids and lipids that are important components of the cell. Demand for amino acids as the building blocks for protein synthesis in rapidly dividing tumor cells is often much higher than that of normal cells. Such increased demand can represent a vulnerability of the tumor. Importantly, this vulnerability is already being exploited for therapy in one instance: Addition of L-asparginase - an enzyme lowering the concentration of the amino acid asparagine in blood - to chemotherapy against acute lymphoblastic leukemia, resulted in a dramatic increase in cure from 5% to 95% of patients treated. Recent scientific publications highlight the fact that tumors are often metabolically rewired, and multiple examples of altered amino acid demand and/or turnover have been demonstrated in different cancer indications. Multiple drugs are under development that target amino acid availability, uptake or biosynthesis.

The challenge is to identify the potential sensitivity of individual tumors to such drugs.

Recently, we developed diricore, a procedure for determination of restrictions in the availability of particular amino acids for protein synthesis. To demonstrate the potential for diricore’s diagnosis capability in cancer, revealing proline limitations for protein synthesis in kidney cancer. We also used kidney cancer cell lines to verify sensitivity to proline deprivation, suggesting therapeutic possibilities.

We propose here to develop diricore towards a commercial diagnostic platform for determining limiting amino acid availability profiles in cancer patients. This information will guide physicians in taking dietary measures or prescribing drugs that inhibit amino acid uptake or biosynthesis.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

ERC-POC - Proof of Concept Grant

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2014-PoC

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Host institution

STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
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.

€ 149 500,00
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.

€ 149 500,00

Beneficiaries (1)

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