Targeting the redox homeostasis: A promising strategy to improve radiosensitivity of colorectal cancer.

Activity: OtherWritten proposal

Description

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.
Period1 Nov 20211 Nov 2022
Held atKOTK - Kom op tegen Kanker-vzw, Belgium
Degree of RecognitionNational