CORDIS
EU research results

CORDIS

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Identification and functional validation of drugable targets/pathways for triple negative breast cancer

Project information

Grant agreement ID: 322737

Status

Closed project

  • Start date

    1 April 2013

  • End date

    31 March 2018

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 2 495 101,56

  • EU contribution

    € 2 495 101,56

Hosted by:

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM

Netherlands

Objective

Patients suffering from triple-negative breast cancer (TNBC) have a poor prognosis as these tumors frequently confer resistance against chemotherapeutic agents and lack drug targets such as estrogen receptor, progesterone receptor, and epidermal growth factor receptor 2. Insufficient knowledge on the biology of this specific breast tumor type and its heterogeneity hinder the identification of potential novel drug targets. Lethality enhancer screening is an ideal approach to identify new drug targets in tumors with specific genetic aberrations. We plan to adapt this concept of synthetic lethality by anticipating that while TNBC cells confer resistance to available anticancer drugs, specific knock down of particular genes by RNA-interference (RNAi) may result in a synergistic cell killing. Another important aspect of our approach is that we will concentrate in our screens on the top 500 candidate genes shown to be crucial in TNBC for cellular processes. The genes will be prioritized by Bayesian network analysis on prior knowledge on clinical TNBC from our own extensive genomics and proteomics studies, the literature, next generation sequencing efforts, and databases listing drugability of targets. We will employ RNAi-based knock down of drugable targets in 22 cell lines to reveal genes essential for drug resistance in TNBC. In addition to 2D cultures, screens will also be applied to 3D cultures, which are thought to better reflect the in vivo situation. The most effective combinations for each TNBC subtype will further be functionally investigated in vitro and in vivo to unravel the molecular nature of the synthetic lethality. Finally, translational studies will be performed to establish the potential clinical relevance of the identified targets/pathways in large numbers of human TNBC and non-TNBC tumors on tissue microarrays. It is expected that the newly designed (combination) therapies result in a decline in TNBC mortality and reduction of healthcare costs.

Principal Investigator

Johannes Albert Foekens (Prof.)

Host institution

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM

Address

Dr Molewaterplein 40
3015 Gd Rotterdam

Netherlands

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 829 673,41

Principal Investigator

Johannes Albert Foekens (Prof.)

Administrative Contact

Auritima Jorge Ribeiro (Ms.)

Beneficiaries (3)

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM

Netherlands

EU Contribution

€ 1 829 673,41

UNIVERSITEIT LEIDEN

Netherlands

EU Contribution

€ 569 044,15

STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS

Netherlands

EU Contribution

€ 96 384

Project information

Grant agreement ID: 322737

Status

Closed project

  • Start date

    1 April 2013

  • End date

    31 March 2018

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 2 495 101,56

  • EU contribution

    € 2 495 101,56

Hosted by:

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM

Netherlands