C2TSG-based Targeted Therapies

Class II tumor suppressor genes (C2TSGs) are epigenetically silenced in a high percentage of most human tumors, including breast and pancreatic cancers. These genes have classically not been considered suitable therapeutic targets, as the therapeutic goal would be to upregulate their expression rather than downregulate or inhibit them. This is of course a more complex approach than inhibiting the target and cannot be achieved by conventional drugs such as antibodies or small molecule inhibitors.

However, nowadays it is possible to search for biological agents or small molecules that can functionally replace (or mimic) the lost tumor suppressor function. Our research group has identified several new C2TSGs in breast cancer, the loss of which is closely associated with a more aggressive tumor type and disease progression. We hypothesize that the functional restoration of these C2TSGs by mimetic drugs represents a new innovative way to treat cancer, a concept that we recently published as a white paper (https://pubmed.ncbi.nlm.nih.gov/36139547/). In addition, this concept was recently presented at the 36. Deutscher Krebskongress 2024 (DKK2024) in Berlin within the Session "Best of Abstracts" by Prof. Edgar Dahl (photos).

An example of 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 Innovation Fund and the recent project acquisition 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/).