Cancer Research Domestic Cats May Help to Understand Breast Cancer in Humans

Study shows that some of the genetic changes in cats tumors resemble closely to those found in human cancers. These parallels open new perspectives for developing targeted cancer therapies, particularly for breast cancer.

Bern/Switzerland – An international research team, with participation of the University of Bern, has conducted the world's first comprehensive genetic study of cancer in domestic cats. The study shows that some of the genetic changes in cat tumors closely resemble those found in human cancers. These parallels open up new perspectives for developing targeted cancer therapies, particularly for breast cancer.

Domestic cats are the second most prevalent pet globally after dogs. According to estimates, around 25 percent of households in Switzerland alone own a cat, and up to 1.5 million animals were living in the country last year. As in humans, cancer is one of the leading causes of illness and death in cats. While research into the genetic basis of cancer in both humans and dogs has made great progress in recent years, cancer research in cats is still in its infancy. This study aims to change that and demonstrates how, in line with the “One Health” approach, findings from veterinary medicine can inform human medicine – and vice versa.

In a large-scale comparative analysis, researchers from the Institute of Animal Pathology at the Vetsuisse Faculty of the University of Bern, the Ontario Veterinary College (Canada) and the Wellcome Sanger Institute (UK) examined the genomes of various cancer types in cats in unprecedented detail. They identified genetic changes that drive cancer development in cats and show remarkable similarities to those in human cancer. The results of the world's first study of this kind were recently published in the journal "Science".

From veterinary medicine to cancer research in humans

The study is based on the genetic analysis of 13 different types of cancer in cats. Researchers analyzed leftover normal and cancerous tissue samples collected during routine treatment from nearly 500 cats across five countries. Sven Rottenberg, senior co-author of the study and Director of the Institute of Animal Pathology at the Vetsuisse Faculty of the University of Bern, explains: "Although domestic cats are common pets, little has been known about the genetics of cancer in these animals. Because they share our households and environmental exposures, studying cat cancers within a “One Health” framework can reveal how environmental factors influence cancer risk and why cancer develops in both cats and humans.”

The researchers analyzed around 1,000 genes that are direct counterparts of known human cancer-related genes and compared the key mutations in these genes across cats, dogs and humans. The Compath platform based at the University of Bern, together with expertise in the field of data-driven precision medicine at the Bern Center for Precision Medicine (BCPM) played an important role in analyzing the feline mammary tumors. The expertise of Sven Rottenberg's group was crucial for validating the results. The team is an international leader in the development and application of three-dimensional cell culture models of mammary tumors, known as Mam tumoroids.

Cats and humans share striking similarities in cancer mutations

The study provides the world's first freely accessible database for future research into the genetics of feline cancer. The analyses revealed that TP53 is the most frequently mutated gene in cat cancer, similar to humans. Chang He, co-first author of the study and a PhD student at the Institute of Animal Pathology at the Vetsuisse Faculty of the University of Bern, says: "We were able to show for the first time that certain genetic changes promote cancer development in cats. Some of these changes also occur more frequently at the same positions in the genome of cats and humans, at so-called mutation hotspots."

The genetic analyses also revealed some unexpected findings, for example in mammary tumors. Rottenberg explains: "We already knew that mammary tumors in cats resemble the phenotype of triple-negative human breast cancer. We therefore suspected that cats also have the known Brca1 mutation. Surprisingly, however, this was not the case." Instead, the researchers primarily found changes in the FBXW7 gene, which is also associated with an unfavorable prognosis in human breast cancer.

In an earlier study, the Rottenberg group had found that human leukemia cells with the inactive FBXW7 gene are particularly responsive to certain anti-cancer drugs such as vinca alkaloids. Building on this knowledge, the Bernese team tested these drugs on Mam tumoroids. "In vitro, vinca alkaloids were markedly more effective in feline tumoroids with FBXW7 mutations compared to tumoroids without these mutations," says Chang He. He adds: "It would be very interesting to investigate the efficacy of these drugs in FBXW7-mutated mammary tumors in a clinical setting in the future. Our Mam tumoroids provide a powerful tool for identifying new or individualized therapeutic options against cancer in both humans and cats."

Comparative cancer research through the "One Health" approach

The results suggest that cats with FBXW7-mutated tumors may serve as a model for a clinically relevant subset of breast cancer in humans - an area in which the University of Bern has been conducting research for years. Louise Van Der Weyden, lead senior author at the Wellcome Sanger Institute in Cambridge (UK), says: "For the first time, data on the genetic causes of feline cancer are now available. This could not only improve the treatment of feline tumors but also open up new possibilities for clinical studies on cancer in humans." Rottenberg summarizes: "With this study, we are building an important bridge between veterinary and human medicine. It impressively showcases the potential of the “One Health” approach – to improve the health of animals and humans alike."

The study was funded by the Swiss National Science Foundation, the Everycat Health Foundation, CVS and the Wellcome Trust.

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