Cancer Research and Animal Models

The second edition of the National Day for Laboratory Animals was held on Saturday, 15 June. This event was promoted by the Swiss Association of Veterinarians in Industry and Research (SAVIR) in collaboration with the Swiss Laboratory Animal Science Association (SGV) and Forschung für Leben (FfL). The goal was to provide transparent information about animal experimentation and to raise awareness about its ongoing importance for scientific research. This year, the focus was on cancer research. It's worth noting that USI, along with other universities and Swiss organisations, adheres to the Swiss Transparency Agreement on Animal Research (STAAR). In relation to this, we are pleased to present an interview with Professor Francesco Bertoni, Vice Director of the Institute of Oncology Research (IOR, affiliated with USI) and Head of the Lymphoma Genomics Group.

Professor Bertoni, what research is your laboratory currently conducting?

Our research focuses on lymphomas, a type of malignant tumour originating from lymphocytes, which usually protect us from infections and the onset of tumours. Specifically, we have two research lines. We are interested in new therapies and the resistance mechanisms that tumour cells use to survive the treatments given to patients. This is because, unfortunately, too many people who develop lymphoma have a disease that either does not respond to treatment right from the start or, especially over time, stops responding to treatment.

We also study a particular type of lymphoma, extranodal marginal zone lymphoma, which often arises following chronic infections or autoimmune inflammation and occurs in anatomical sites that are not lymph nodes or bone marrow, typical of other lymphomas.

What are the most promising leads?

We are working on various approaches for new treatments, including small molecules, antibody-based therapies, and cell therapies. We are obtaining very interesting information by maintaining lymphoma cell models, derived from patients, under treatment for several months until resistance develops. In parallel, we use genetic engineering approaches that allow us to study the effects of all genes or non-coding transcripts by turning them on or off one at a time in cells exposed to the drug we are studying. These methods help us understand how the drug works, how we can enhance its effectiveness, and which patients are most likely to benefit from it.

In our study of extranodal marginal zone lymphoma, we are employing techniques that allow us to observe the genes expressed and their regulation at the individual cell level, as well as within the surrounding microenvironment cells.

Could you advance in your research without animal experimentation?

Our work primarily uses in vitro models and aims to minimise animal testing by substituting it with other methods whenever possible. However, the complete elimination of animal testing is not yet feasible for advancing our research on lymphoma. We use murine models to grow human or murine tumour cells to validate new drugs' in vitro observed antitumor activity, whether used individually or in new combinations. This is necessary because relying solely on in vitro cell lines might overstate a treatment's effectiveness. Additionally, we utilise murine models to assess the effects of drugs on both tumour cells and immune system cells. To address these needs, we have begun implementing methods that allow us to cultivate tumour cells along with various other cells, including immune system cells, in vitro. This approach will help us further minimise the use of mouse experimentation.

Interestingly, in our field, domestic dogs have a high incidence of spontaneous lymphomas, which are biologically similar to humans. We are thus collaborating with veterinarians to compare the genetics and drug response between canine and human tumours. This will provide valuable data for humans without having to recreate the situation in the lab, i.e., without having to reproduce the tumours in mice, while also offering new therapies to animals in need.