First atlas of mouse cancer cell lines developed

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CONICET scientist Daniel Alonso participated in the development of this initiative, which seeks to be a contribution to the development of new therapeutic strategies against tumors in humans. The new tool has already been used in a paper published in Nature that addresses the specific relationships between an important oncogene and the development of cancer in different tissues.

The image shows how the KRAS oncogene drives cancer progression differently in each organ. Image credit: Sebastian Mueller, Roland Rad et al.

An international scientific team, including CONICET researcher Daniel Alonso, director of the Center for Molecular and Translational Oncology (COMTra-UNQ), has just released the first Mouse Cancer Cell line Atlas. This valuable tool, useful for understanding how different types of cancer develop and can be treated in humans, has as its first fruit a work published in the prestigious journal Nature, which analyzes the specific relationships between the KRAS gene (which appears mutated in many types of cancer) and the development of tumors in different organs.

Mouse models of cancer and other diseases have become indispensable resources and a source of key discoveries for understanding their mechanisms of action, as well as for the development of new treatments.

In this sense, the new Atlas is a curated collection of cancer cell lines in mice, with almost 600 specimens, covering dozens of types of cancer, including all the most prevalent. It forms a huge open database, accessible to scientists from all over the world, with complete genetic information, histopathological and immunological studies and comparative analyses with homologous tumors in humans.

**“Until now, although there were collections of human cell lines, there was no resource of these characteristics for cancer in mice, which is the most widely used experimental model in biomedical research and the one that best reproduces the disease in humans,” said Alonso.

The development of the Atlas was led from Germany by scientists Sebastian Mueller and Roland Rad, from the Munich School of Medicine and Health and the Heidelberg Cancer Research Center, who gathered the collection of cell lines by convening researchers from other centers in Germany, the United Kingdom, Canada, the United States, Spain, Italy and Argentina.

“My contribution included a cell line of an aggressive cancer, which we isolated more than three decades ago during my doctoral thesis together with researcher Elisa Bal at the Roffo Oncology Institute (UBA) and validated as a model during all these years at the National University of Quilmes (UNQ). I serve as the Latin American contact for this international initiative,” *Alonso said.

The KRAS oncogene in different cancers
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In the study recently published in Nature (of which Alonso is also one of the authors), the atlas was used as a tool to study the specific evolution of cancers in each tissue under the impulse of the KRAS oncogene.

Oncogenes are genes that are altered in cancer cells, resulting in an altered protein that overstimulates the growth of that cell. RAS oncogenes, and particularly KRAS, are the most frequently affected in human cancer. However, when cancer occurs, several genes are altered in the same cell population to give rise to the disease and the evolution is highly variable in each tissue.

“Oncogenes such as KRAS show great specificity depending on the tissue in which they act; Its ability to cause cancer, genetic interactions, and effects on cells vary greatly, but the reasons behind this are still not entirely clear. In some ways, the precise links between the mutated oncogene and cancer progression, to the complex changes in cellular behavior that lead to cancer in one tissue, but not in others, constitute a ‘missing link’ to better address prevention and treatment,” Alonso said.

The study made it possible to analyse these questions in types of cancer strongly associated with the KRAS oncogene, such as pancreatic, lung and intestinal cancer. “In addition, as these evolutionary processes begin to be understood in these mouse cell lines, the model studied itself is a ’test bed’ to advance towards new therapeutic approaches for human cancer. In fact, part of the study sought the parallelism of the results with clinical data,” added the CONICET researcher.

Although people usually have two copies or alleles of each gene in their DNA (one on the maternal side and one on the paternal side), mutations in KRAS can cause copies of this gene to multiply in affected cells. In this sense, the study shows, among other issues, that this increase in the number of genetic copies of mutated KRAS has specific effects depending on the type of cell and that determines when cancer can arise in each tissue. In the case of the pancreas, the increase causes a ‘reprogramming’ of cellular behavior very early in the cancerous transformation. In intestinal tissue, an early blockade of cell specialization is observed, which generates the conditions for the generation of other mutations that collaborate with the KRAS oncogene.

“More generally, these findings begin to shed light on the innate and acquired factors that guide the evolution of cancer in different tissues, and may eventually establish more predictable molecular patterns and temporal dynamics, with expected results in the cell compartment. It is an important advance towards a mechanistic understanding of the always complex and unstable cancerous genomes,” concluded Alonso.

According to the researcher, one of the group’s next objectives is to promote the use of the platform offered by the Atlas and to continue gathering wills from all corners of the world, to continue unveiling the knowledge gaps that still persist in all types of tumors.

Citation
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The article A disease model resource reveals core principles of tissue-specific cancer evolution was published in Nature magazine. Authors: Sebastian Mueller, Niklas de Andrade Krätzig, Markus Tschurtschenthaler, Miguel G. Silva, Chiara Thordsen, Riccardo Trozzo, Perrine Simon, Frederic Saab, Thorsten Kaltenbacher, Magdalena Zukowska, Daniele Lucarelli, Rupert Öllinger, Joscha Griger, Nina Groß, Tanja Groll, Jessica Löprich, Antonio E. Zaurito, Linus R. Schömig, Jeroen M. Bugter, Stefanie Bärthel, Chiara Falcomatà, Alexander Strong, Cordelia Brandt, Mulham Najajreh, Aristeidis Papargyriou, Roman Maresch, Katharina A. N. Collins, David Sailer, Christian Schneeweis, Sebastian Burger, Lisa M. Fröhlich, Christine Klement, Alexander Belka, Juan J. Montero, Ute Jungwirth, Maximilian Reichert, Markus Moser, Jens Neumann, George Vassiliou, Juan Cadiñanos, Ignacio Varela, Carsten Marr, Daniel F. Alonso, Pier-Luigi Lollini, Jean Zhao, Louis Chesler, Clare M. Isacke, Angela Riedel, Christian J. Braun, Martin L. Sos, Filippo Beleggia, Hans C. Reinhardt, Monica Musteanu, Mariano Barbacid, Michael Quante, Marc Schmidt-Supprian, Günter Schneider, Simon Clare, Trevor D. Lawley, Gordon Dougan, Katja Steiger, Nathalie Conte, Allan Bradley, Lena Rad, Dieter Saur & Roland Rad

Mueller, S., de Andrade Krätzig, N., Tschurtschenthaler, M. et al. A disease model resource reveals core principles of tissue-specific cancer evolution. Nature (2026). https://doi.org/10.1038/s41586-026-10187-2