Triapine belongs to a group of substances known as thiosemicarbazones. These substances target the weak points of cancer cells, in particular their high demand for certain metals such as iron. However, the new study shows that triapine can do even more: it triggers what is known as “immunogenic cell death.” This causes tumor cells to die in a way that alerts and activates the immune system. This means that the body itself begins to fight the tumor.
When tumor cells are destroyed by triapine, they release certain signals that attract immune cells, especially the so-called CD8+ T cells, which are known as “killer cells.” These cells specifically attack the tumor cells and can even develop a kind of “memory” to keep the cancer at bay in the long term.
This effect is supported by another important mechanism: the activation of the so-called FAS-signaling pathway. Triapine increases the amount of FAS on the surface of tumor cells. This protein acts like a “switch” that makes tumor cells more susceptible to attacks by the immune system.
Experiments with mice have shown that cancer cells treated with triapine train the immune system to respond more quickly and effectively when confronted with cancer cells again. This led to delayed tumor formation and, in many cases, even complete protection against renewed tumor growth.
The study highlights that the already clinically tested triapine is a promising candidate for combination with immunotherapies. Through its dual action—directly targeting cancer cells and activating the immune system—triapine could significantly improve the effectiveness of existing cancer therapies.
This research, funded by the Austrian Science Fund (FWF) and the City of Vienna, underscores the importance of collaboration between chemistry, biology, and medicine in developing innovative approaches to cancer treatment. The findings demonstrate the importance of incorporating the immune system into cancer therapy and open up new perspectives for personalized medicine.
Publication: Experimental Hematology and Oncology
The anticancer thiosemicarbazone triapine exerts immune-enhancing activities via immunogenic cell death induction and FAS upregulation.
Stiller B, Stefanelli A, Schueffl H, Mathuber M, Skorokhyd N, Gufler J, Pirker C, Holcmann M, Panchuk R, Sibilia M, Marko D, Berger W, Kowol CR, Hager S, Heffeter P.
DOI: 10.1186/s40164-025-00700-0.
https://ehoonline.biomedcentral.com/articles/10.1186/s40164-025-00700-0