Targeting ZEB pathways to tackle aggressive (colorectal) cancer (ZENTACC). (ZENTACC)

Colarectal cancer (CRC) is a disorder with a heterogeneous disease outcome but is usually lethal in case of tumor metastasis. Patients can be divided into four different consensus molecular subtypes (CMS) with clearly distinguishable characteristics.

The SBO consortium has gained new insights through the identification of the transcription factors ZEB1 and ZEB2 as oncogenes in malignant CRC and other aggressive cancer types. For CRC, this mechanism can be associated with the subgroup of CRC patients with a very poor prognosis (100% 5-year mortality). Very recent data obtained by the Berx and Van Loo research groups showed that there is a key role for the intestinal microbiota in the initiation and progression of ZEB2-induced CRC.
To date, there are no drugs on the market that have the reduction / ablation of ZEB1 / 2 driven cancer stem cells (CSCs) or the control of malignant EMT as a mechanism of action. Nonetheless, such drugs would have an important clinical value in combination with existing therapeutics. Neither are there reliable and clinically validated biomarkers for the diagnosis or follow-up of these aggressive ZEB1 / 2-positive cancers.