C2TSG-based Targeted Therapies

Class II Tumor Suppressor Genes (C2TSGs) become epigenetically silenced in a high percentage of most human tumors including breast and pancreatic cancer. These genes have classically not been considered as suitable therapeutic targets, since upregulation of their expression and not down-regulation or inhibition would be the therapeutic goal. This is of course a more complex approach than target inhibition and cannot be achieved through conventional drugs like antibodies or small molecule inhibitors.

However, nowadays it has become possible to screen for biologicals or small molecules that can functionally substitute (or mimic) the lost tumor suppressor function. Our research group has identified several new C2TSGs in breast cancer, their loss being closely associated with a more aggressive tumor type and disease progression. We expect that the functional restoration of these C2TSGs by mimetic drugs represents a new innovative way to treat cancer, a concept, we have recently published as a white paper (https://www.mdpi.com/2072-6694/14/18/4386).

An example for a very strong C2TSG in breast (and bladder) cancer is the ITIH5 gene (see Rose et al. 2017; https://www.ncbi.nlm.nih.gov/pubmed/28231808 and Rose et al. 2021; https://pubmed.ncbi.nlm.nih.gov/33924987).

With initial support from the RWTH Aachen Innovationsfonds and recent project takeover by the RWTH spin-out project Qithera, we are characterizing ITIH5 polypeptides that can mimic the tumor-suppressive function of ITIH5 (https://pubmed.ncbi.nlm.nih.gov/35158755/).