Preventing Therapy Resistance in Esophageal Cancer using Advanced Models
and Molecular Signatures (PRESSURE)
Esophageal cancer is one
of the most therapy resistant cancers and in dire need of improved treatments.
The PRESSURE consortium will address key challenges that preclude the effective
treatment of this disease. This includes the identification of resistance
mechanisms using relevant models for EAC and biomarker tools. This knowledge is
used to modify or repurpose currently available modalities. In particular, it
is aimed at shortlisting candidate genes or signaling pathways that underpin
resistance, and are considered for targeting. A strong focus will be on the
combination or repurposing of compounds, also from non-oncological indications.
We will explore and validate candidate therapeutic targets in a standardized
EAC model panel, but also expanding it to ex vivo 3D models, including spheroid
cultures (based on standard cell lines, primary cells, and PDXs), mixed
spheroid cultures (spheroids including fibroblasts, endothelial cells, and immune
cells) and, in particular, ex vivo tissue slice cultures derived from EAC PDXs.
