UNBRACE TERMINATED

Project "UNBRACE" data sheet

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 Partnership

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 Project objective

BRAF mutant (MT) colorectal cancer (CRC) accounts for 10-15% of CRC and represents the subgroup with the worst overall survival. There is an urgent need to identify strategies that hit the 'Achilles Heel' in poor prognostic BRAFMT CRC. Preliminary data from the host lab have shown that BRAFMT CRC cells are vulnerable to disturbances in the Endoplasmic Reticulum (ER)-specific Unfolded Protein Response (UPR) machinery. The overall aim of the proposal is to identify whether the ER stress activator ONC201 in combination with MAPKi (MEK1/2i or BRAFi) will be a novel treatment strategy for BRAFMT CRC.

Specific objectives of the proposal are 1. Investigate the effect of ONC201 combined with MAPKi in BRAFMT CRC in vitro. 2. Investigate the in vivo effect of ONC201 with MAPKi using BRAFMT CRC syngeneic and patient derived xenograft models. 3. Assess prognostic/predictive role of ER stress proteins in CRC.

UNBRACE will go beyond the current state-of-the-art by (i) developing a novel treatment strategy targeting the biology of poor prognostic BRAFMT CRC; (ii) using relevant pre-clinical models and clinical available datasets to underpin a novel stratified solution for BRAFMT CRC with poor clinical outcome. UNBRACE adopts the concept “personalized medicine strategy” through applying a novel approach targeting BRAFMT CRC.

This fellowship will provide the researcher, through mobility, an increased set of excellent skills (e.g. molecular pathology; patient derived xenografts, 3D organoids), which will give him the opportunity to become a future leader in experimental cancer medicine.

The fellowship will result in a strong collaborative network between the host and partner institute, transfer of knowledge between academia and industry, ultimately resulting in a phase I clinical trial in BRAFMT CRC. The fellowship can form the basis to attract other scientists internationally, from other disciplines and sectors to receive training in these unique R&I skills.