Abstract 72P
Background
Repurposing of approved or investigational drugs used outside the field of oncology presents an attractive strategy to improve cancer treatment. According to World Health Organization (WHO), colorectal cancer (CRC) is the third most common cancer type and is the second leading cause of cancer-related death worldwide. Current CRC treatments are largely limited to surgery, either alone or in combination with chemotherapy or targeted therapy, depending on tumor stage.
Methods
To address this therapeutic gap, we developed a semi-automated drug screening assay based on a drug repurposing approach. Using this strategy, we screened a drug library of more than 1200 FDA-approved and experimental compounds on two CRC cell lines: BRAF-mutant HT29 and KRAS-mutant HCT116. To better replicate the physiology of human tumors, 3D spheroid cultures of HT29 and HCT116 cells were grown on Matrigel pre-coated plates.
Results
Our screen identified more than 40 potential drug candidates per CRC cell line, which were further evaluated for their half-maximal inhibitory concentration (IC50) values. Additionally, we validated their anti-tumor activity on patient-derived CRC organoids. Studies to assess the impact of the drug candidates on tumor growth in different CRC mouse models are ongoing.
Conclusions
Altogether, this work provides a proof of concept for a successful drug repurposing strategy that will help contribute to the development of more targeted therapies and potentially benefit other cancer types.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Luxembourg National Research Fund (FNR).
Disclosure
All authors have declared no conflicts of interest.