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Identification of the proteasome machinery targets in human cancer

Objective

The 26S/20S proteasome and immunoproteasome machinery is the major protein degradation system in human cells and a strongly oncogenic factor upregulated in most human neoplasias of various tissues. Thus, it is a target of clinically approved treatment protocols in human multiple myeloma and mantle cell lymphoma. However, clinical trials have shown a limited effect of proteasome inhibitors in solid tumors and their metastases, despite initial encouraging results in vitro and in xenografts.

The main objective of the following project is to understand the oncogenic contribution of the human proteasome machinery to the proteome and transcriptome of human cancer cells and to use this knowledge to improve the anti-cancer therapeutic approaches targeting the proteasome and its downstream effectors, in human cancer types causing most deaths in the European Union – lung, colon/rectum and pancreatic cancers.

The main research hypothesis is that the unknown mechanisms downstream of the human proteasome machinery are critical for cancer progression and will be effective as drug targets in the treatment of the solid tumors and their metastasis. Discovering these mechanisms using proteome-scale mass spectrometry analysis combined with RNA-sequencing will allow in this project to:
(i) identify novel proteasome targets and understand reprogramming of human neoplastic cells by the proteasome machinery on the basic level in multiple myeloma, lung, colon and pancreatic cancer cultured cells,
(ii) understand the reason for the exceptionally efficient therapeutic effect of the proteasome inhibitor carfilzomib in multiple myeloma compared to solid tumor cancer cells, and
(iii) test in frozen/fixed tumor material, cell cultures the functional validity of the discovered proteasome targets as therapeutic target candidates in lung, colon and pancreatic cancers – which could increase efficiency or bypass targeting of the proteasome machinery by carfilzomib in the solid tumors

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.

MSCA-IF-EF-ST - Standard EF

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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) H2020-MSCA-IF-2017

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Coordinator

INSTYTUT MEDYCYNY DOSWIADCZALNEJ I KLINICZNEJ IM MIROSLAWA MOSSAKOWSKIEGO POLSKIEJ AKADEMII NAUK
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.

€ 146 462,40
Address
UL. PAWINSKIEGO 5
02 106 WARSZAWA
Poland

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Activity type
Higher or Secondary Education Establishments
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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.

€ 146 462,40
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