Researchers at the University of Geneva (UNIGE) have developed in vitro models of the kidneys, liver and heart for the purposes of testing the effects of new cancer treatments on healthy tissue.
Acquired resistance, when tumours develop resistance to cancer treatments, represents a major challenge in oncology. While combination therapies have shown great promise in overcoming that resistance, they are often highly toxic to healthy organs and tissues. The UNIGE team’s new laboratory platform allows for the rapid testing of drug effects without the need for animal models.
Patrycja Nowak-Sliwinska, associate professor in the School of Pharmaceutical Sciences at the UNIGE Faculty of Science, said: “This platform models the human kidney, heart and liver in vitro, as clusters of cells derived from human tissue.
“[It enables us to] study how new drug combinations interact with these organs and then decide whether it is justified to move on to in vivo testing in humans or animals.”
The research, published in Biomedicine and Pharmacotherapy, focused on the kidneys, liver and heart – three organs that are particularly sensitive to combination therapies. Scientists from the School of Pharmaceutical Sciences, in collaboration with the UNIGE Faculty of Medicine and Geneva University Hospital (HUG), tested two drug combinations currently in development, C2 (erlotinib HCl, dasatinib, tubacin, tacedinaline) and REMP (erlotinib HCl, parthenolide, metformin HCl, RAPTA-C).
In one notable finding, they discovered that C2 demonstrated significant liver toxicity, showing that in vivo testing may not be appropriate for this combination.
Another advantage of this new approach is that it takes only two weeks to obtain results, whereas animal models take around ten weeks or more.
The researchers noted: “In addition to saving a significant amount of time, this approach is fully in line with the 3R principle, which aims to ‘reduce’, ‘replace’ and ‘refine’ the use of animal models in research.”
The next step in the research will be to extend the model to other treatment-sensitive organs. The researchers hope to one day move beyond standard cell lines and instead use patient-derived cells, allowing drug combinations to be tested for toxicity in a personalised context.