Thomas Helleday Group
The overall aim of the Helleday laboratory is to improve the treatment of cancer by exploiting cancer defects in order to tailor specific drugs for all types of cancer, with minimal side-effects.
The Helleday lab is a multidisciplinary translational research group focusing on understanding basic DNA repair and DNA-damage signaling pathways at replication forks and developing novel drugs for anti-cancer treatments. The research covers both basic and translational work including academic-driven clinical trials, based on basic science findings from the laboratory.
Professor Thomas Helleday is The Torsten and Ragnar Söderberg Professor of Translational Medicine and Chair in Chemical Biology at Karolinska Institutet, Stockholm, Sweden.
For more detailed information about our lab visit helleday.org
Many DNA damaging anti-cancer drugs cause replication-associated DNA damage that kill cancer cells. This is an effective way of treating cancer, but the problem is that also normal cells are damaged. Our strategy is to exploit the high level of DNA damage in cancer cells and prevent the repair of these lesions. Using DNA repair inhibitors, we can selectively introduce toxic DNA damage to cancer cells.
Our idea is based on three strategies:
1) Basic science understanding on DNA replication repair.
Basically all potentially curative anti-cancer treatments work by causing DNA damage. This damage is normally not lethal but is converted into lethal lesions upon DNA replication. Cancer cells have numerous co-ordinated DNA repair pathways operating in replicating cells and our strategy is to gain in depth knowledge into these processes, giving us insights into how genome stability is maintained and also identifying putative targets for anti-cancer treatment.
2) DNA repair pathways operating in cancer patients.
It is critical that we work closely with patients and investigate if DNA repair pathways identified in basic science are operating in cancer specimen and what their roles are in this context. Therefore, we conduct our experiments in collaboration with cancer patients, to see which DNA repair pathways are relevant in their individual cancers.
3) Small molecule inhibitors to selectively kill cancer cells.
Once we gain understanding of repair processes in cancer we purify putative DNA repair proteins and identify small molecule inhibitors. These are further improved to effectively and selectively inhibit the protein in cells. Ultimately, we progress these small molecules and test in cancer patients in clinical trials to determine if we are able to improve current anti-cancer treatments.