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Triple negative breast cancer control through synergistic inhibition of EGFR and CDK9 signaling

Objective

"Triple negative breast cancer (TNBC) is an aggressive disease, accounting for 15-20% of breast cancer cases, but disproportionally causing breast cancer-related death. TNBC does not express the targetable receptors ER, PR, and HER2 that are known to drive other forms of breast cancer. Mainstay practice for TNBC in the clinic is to treat with non-targeted cytotoxic chemotherapies. Long-term outcomes are however still poor, most likely owing to intrinsic drug resistance. Clinical trials have attempted to explore molecular targeted therapies to block dysregulated growth factor receptors in TNBC, for instance, epidermal growth factor receptor (EGFR), as it is overexpressed in ~80% of TNBC. Yet, giving the long-standing availability of clinically approved EGFR-targeted therapies, such as lapatinib, the clinical benefit of single agent therapy is unsatisfactory, owing to the compensatory dysregulated signaling pathways. In our ongoing ERC – Advanced Grant Triple-BC (#322737) we are striving to explore combinatorial molecular targeted therapies to concomitantly block the identified dysregulated signaling pathways. Our preliminary work revealed that an inhibitor targeting cyclin-dependent kinase 9 (CDK9) strikingly synergized with targeting EGFR receptor family signaling to inhibit cell proliferation of TNBC cell lines. The overall goal of this PoC project is to exploit this novel finding and provide proof-of-concept evidence that stalling CDK9 signaling may enable successful targeted combination therapy in TNBC. Therefore, the specific objective is to assess the pharmacological response of dual EGFR-CDK9 targeting in TNBC patient-derived xenograft (PDX) mouse models in vivo. We envisage that this PoC project will translate our identified successful synergistic treatment into an effective future novel and safe combinatorial targeting strategy benefiting TNBC patients."

Fields of science (EuroSciVoc)

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Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

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-2017-PoC

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Host institution

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
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.

€ 90 075,00
Address
DR MOLEWATERPLEIN 40
3015 GD Rotterdam
Netherlands

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Activity type
Higher or Secondary Education Establishments
Links
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.

€ 90 075,00

Beneficiaries (2)

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