C2TSG-based Targeted Therapies

Class II Tumor Suppressor Genes (C2TSGs) become epigenetically silenced in a high percentage of different human tumors like breast cancer, colon cancer and lung 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 protein 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.

With support from the RWTH Innovationsfonds we have started to generate and characterize ITIH5 peptides that can mimic the tumor-suppressive function of the ITIH5 gene (see Rose et al. 2017; https://www.ncbi.nlm.nih.gov/pubmed/28231808), the latter being frequently inactivated by DNA hypermethylation in breast cancer (Veeck et al 2008; https://www.ncbi.nlm.nih.gov/pubmed/17653090).