Cancer Research and Animal Models

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On Saturday, June 15th, the second edition of the National Day of Information on Laboratory Animals will be held. This event is promoted by the Swiss Association of Veterinarians in Industry and Research (SAVIR) in collaboration with the Swiss Society for Laboratory Animal Science (SGV) and Forschung fr Leben (FfL). The aim is to provide transparent information on animal experimentation and raise awareness about its ongoing importance for scientific research. This year’s theme is cancer research. Remembering that USI, along with other universities and Swiss organizations, adheres to the Swiss Transparency Agreement on Animal Research (STAAR), we present an interview with Professor Francesco Bertoni, Deputy 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 tumor that originates from lymphocytes, the cells that usually protect us from infections and also from the onset of tumors. Specifically, we have two research lines. We are interested in new therapies and the resistance mechanisms that tumor 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 treatments right from the start or, especially over time, stops responding to treatments.

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 avenues?

For new treatments, we are working on various approaches, 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 enable us to understand the mechanisms of drug action, how we can improve their effectiveness, and which patients can benefit the most from them.

To study extranodal marginal zone lymphoma, we are using methodologies that allow us to see expressed genes and how they are regulated at the level of individual lymphoma cells and the surrounding microenvironment cells.

Could you advance in your research without animal experimentation?

We conduct the vast majority of our work using in vitro models and avoid animal testing as much as possible, replacing it with other methods. However, we still cannot completely do without it to progress in our lymphoma research. In our case, we use murine models in which we grow human or murine tumor cells. We sometimes use them to confirm the antitumor activity - previously observed in vitro - of new drugs, given as single agents or in new combinations. This is because relying solely on in vitro cell lines might overestimate a therapy’s effectiveness. Another reason is to study the drugs’ effects not only on tumor cells but also on immune system cells. For both needs, we have already started using methods that allow us to grow tumor cells in vitro along with various other cells, including immune system cells. This will enable us to further reduce the use of mouse experimentation.

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