Colorectal cancer (CRC) accounts for approximately 10% of cancer-related mortality in the western world. Radiotherapy (RT) is a cornerstone treatment of CRC, however a subset of patients does not sufficiently respond. Conventional RT mainly targets DNA via the production of reactive oxygen species (ROS). Cancer cells heavily rely on the antioxidant (AO) system to sustain the delicate balance between ROS production and scavenging. Hence, targeting the redox homeostasis is an attractive strategy to tackle radioresistance. In this project, we aim to enhance the overall responses in CRC by combining cytotoxic and radiosensitizing strategies. CRC cells will be treated with a novel combinatorial regimen, consisting of a HDAC inhibitor (HDACi), which has the potential to induce ROS, combined with a xCT inhibitor, namely sulfasalazine. Both possess intrinsic cytotoxic properties and are clinically available drugs. The repurposing of already available drugs as radiosensitizers will make the transition from bench-to-bedside straightforward. In summary, we hypothesize that by combining a HDACi and a xCT inhibitor the ROS homeostasis will be disrupted sufficiently to obtain lethal ROS levels in the cell upon irradiation, giving an additional anti-tumoral boost to the previous identified cytotoxic properties of both drugs.
|Effective start/end date||1/11/21 → 31/10/22|
Flemish discipline codes
- Other medical and health sciences not elsewhere classified
- Redox Homeostasis
- Colorectal cancer