Colorectal cancer (CRC) is the third most common and second deadliest cancer globally. At advanced stages, it’s typically treated with a chemotherapy combo called FOLFOXIRI, but it comes with significant side effects and varies in effectiveness from person to person.
Cancer cells can become resistant to chemotherapy over time, reducing its effectiveness. Researchers at the University of Geneva (UNIGE) discovered specific lipid changes in chemotherapy-resistant cancer cells. These changes could help predict resistance, leading to personalized treatments to restore drug sensitivity.
Prof. Patrycja Nowak-Sliwinska’s team at the University of Geneva’s School of Pharmaceutical Sciences has tackled chemotherapy resistance in cancer cells through multiple projects. In 2022, they first developed drug combinations that could overcome resistance and then created artificial tumors in 2023 to test treatment effectiveness. Their recent work highlights that cancer cells resistant to FOLFOXIRI exhibit specific changes in certain lipids.
Dr. George M. Ramzy, Research and Teaching Fellow in the School of Pharmaceutical Sciences at the UNIGE Faculty of Science and first author of the study, said, “The identification of altered lipid species could serve as potential prognostic markers of chemotherapy resistance. Understanding these changes may also help develop new treatment strategies to overcome this resistance and play a crucial role in restoring drug sensitivity.”
To achieve these promising results, Prof. Nowak-Sliwinska’s team collaborated with Serge Rudaz’s group from the same school. They studied four cancer cell lines, each from a different patient with a unique genetic profile. Some cells were treated with FOLFOXIRI for up to 60 weeks to mimic the development of resistance seen in actual patients, while others were left untreated.
They then compared the lipid profiles, or “lipidomes,” of the resistant cells to those of the untreated cells. This comparison helped them identify the specific lipid changes associated with chemotherapy resistance.
Dr. Isabel Meister’s team used untargeted lipid profiling involving liquid chromatography and high-resolution mass spectrometry to identify different types of lipids in the cells.
For data analysis, they created a unique algorithm to spot common and specific changes between the lipid profiles of cells sensitive and resistant to FOLFOXIRI. Dr. Julien Boccard mentioned that they handled the complex data effectively using experimental design and factor analysis.
In one cancer cell line, resistance to chemotherapy was linked to higher levels of triglycerides and cholesterol esters. In the other three lines, it was linked to increased phospholipids. These differences are due to each patient’s unique genetic profile, emphasizing the need for personalized treatments.
While these results are promising for creating personalized treatments and restoring chemotherapy sensitivity, they must be tested on fresh tumor samples before being used in clinics.
Journal Reference:
- Ramzy, G. M., Meister, I., Rudaz, S., Boccard, J., & Nowak-Sliwinska, P. (2025). Identification of Lipid Species Signatures in FOLFOXIRI-Resistant Colorectal Cancer Cells. International Journal of Molecular Sciences, 26(3), 1169. DOI: 10.3390/ijms26031169
