This week I had a short exchange on LinkedIn with Brian Krueger, PhD as he was talking about the increasing role of comparative oncology and telling a really personal story on veterinary cancer vaccines (if you missed the post, here the link https://www.linkedin.com/posts/davide-confalonieri-phd_omicly-weekly-50-activity-7264299114249523200-GJoR?utm_source=share&utm_medium=member_desktop ).

Quite often we hear about comparative oncology in Vet Science as a way to get inspiration for new therapies, but as Vet research is catching up, I had to ask myself:

Is this still the case?

After the recent acquisition of Saiba Animal Health AG by Boehringer Ingelheim , bringing Virus-like particles as a new modality in a Big Pharma pipeline, this week we have a great article by Yeganeh Mehrani et al. on the role of Oncolytic Viruses for Mast Cell Tumors.

Is the tide going to turn?

Enjoy this week’s newsletter!

In Vitro

Auranofin Stops Growth and Kills Canine Mammary Tumor Cells by Targeting the PI3K/AKT Pathway

This study, by Lin et al. from Fujian Agriculture and Forestry University, Fuzhou, China , focuses on a drug called Auranofin, which has been found to affect the growth of canine mammary tumor cells. The researchers explored how Auranofin works to stop the cancer cells from growing and how it triggers apoptosis, a process where cells are programmed to die. The study specifically looked at how Auranofin affects a key signaling pathway in cells called the PI3K/AKT pathway. This pathway is involved in cell growth, survival, and division. By blocking or altering this pathway, Auranofin helped stop the tumor cells from growing and led them to die off. The research suggests that Auranofin could be a potential treatment for canine mammary tumors by targeting the PI3K/AKT pathway. It opens the door to further studies that may help develop new cancer therapies for dogs with breast cancer.

Lin, Z., Chen, R., Wang, J., Zheng, Y., He, Z., Yan, Y., Zhang, L., Huang, X. and Zhang, H. (2024), Auranofin Suppresses the Growth of Canine Mammary Tumour Cells and Induces Apoptosis via the PI3K/AKT Pathway. Vet Comp Oncol, 22: 555-565. https://doi.org/10.1111/vco.13005

Exploring Oncolytic Viruses for Treating Canine Mast Cell Tumors

This study by Yeganeh Mehrani et al. from the University of Guelph focuses on mast cell tumors (MCTs), one of the most common types of skin cancer in dogs. While surgery is the primary treatment, some tumors can grow back or spread to other parts of the body, even when they seem less aggressive. The researchers explored the use of oncolytic viruses to treat these tumors. They tested three different viruses on a cell line created from a canine mast cell tumor: Recombinant Vesicular Stomatitis Virus (rVSV-Δm51), Avian Orthoavulavirus-1 (AOaV-1), and Orf Virus. Using advanced laboratory techniques, the team examined how effectively these viruses could infect and kill the tumor cells. Among the three, the rVSV-Δm51 virus showed the strongest ability to destroy cancer cells in lab tests. This study highlights the potential of oncolytic virotherapy as a treatment for canine mast cell tumors, paving the way for further research to determine its effectiveness in real-world clinical settings. The work represents an important step toward developing new, less invasive cancer therapies for dogs.

Mehrani, Y., Kakish, J.E., Napoleoni, C., Thompson, J.J., Knapp, J.P., Minott, J.A., Yates, J.G.E., Stuart, D., Coomber, B.L., Foster, R.A., Bridle, B.W. and Karimi, K. (2024), Characterisation and Sensitivity of a Canine Mast Cell Tumour Line to Oncolytic Viruses. Vet Comp Oncol. https://doi.org/10.1111/vco.13024

How Tilmicosin Works Against Mycoplasma synoviae in Labs and Animals

This study, led by Yab et al. from Foshan University , China, explores how the antibiotic tilmicosin works to fight Mycoplasma synoviae. The researchers focused on two key aspects: (1) Pharmacokinetics (PK): How the drug moves through the body—how it’s absorbed, distributed, broken down, and eliminated. (2) Pharmacodynamics (PD): How the drug affects the bacteria—how much is needed to stop its growth or kill it. They tested tilmicosin both in the lab (in vitro) and in live animals (in vivo) to understand how it works under different conditions. The goal was to figure out the right dose and treatment approach to make the antibiotic most effective while reducing the risk of resistance. The study combines lab and animal testing to better understand how tilmicosin fights infections caused by Mycoplasma synoviae. This research helps optimize its use in poultry farming, improving animal health and minimizing the spread of resistant bacteria.

Yan, Xiu, Jinxin Liu, Weihuo Li, Shuti Song, Zhaofeng Yao, Yixin Jia, Sheng Yuan, Hong Yang and Nan Zhang. 2024. “ The pharmacokinetics/pharmacodynamics integration of tilmicosin against Mycoplasma synoviae in vitro and in vivo.” Journal of Veterinary Pharmacology and Therapeutics 47: 503–511. https://doi.org/10.1111/jvp.13475 .

Role of M-CSF and IL-34 in Canine Bone Cancer and Immune Response

This research, led by Robinson et al. from Louisiana State University , looks at two molecules, M-CSF and IL-34, which play a role in regulating immune cells called macrophages. These molecules are studied in the context of canine osteosarcoma. The focus is on understanding the tumor immune microenvironment, which refers to the interactions between cancer cells and immune cells in and around the tumor. The researchers examined how M-CSF and IL-34 might influence macrophages in this environment, particularly how these molecules may help the tumor grow or evade immune defenses. By studying these immune-related molecules, the research aims to shed light on how osteosarcoma interacts with the immune system. This knowledge could lead to new treatments that target the tumor’s ability to manipulate the immune response, improving outcomes for dogs with osteosarcoma.

Robinson, C.J., Moeller, C.E., Quick, C.N., Goodermuth, C.E., Carossino, M. and Withers, S.S. (2024), Macrophage Colony Stimulating Factor (M-CSF) and Interleukin-34 (IL-34) Expression in Canine Osteosarcoma in the Context of the Tumour Immune Microenvironment. Vet Comp Oncol, 22: 480-489. https://doi.org/10.1111/vco.12993

Diagnostics & Biomarkers

Isolation of Tumor-Derived Particles from Dogs with Brain Tumors: A Pilot Study

This study, by Simona Vincenti et al. from Universität Bern , Switzerland, focuses on understanding how cancer cells from intracranial tumors in dogs release tiny particles called extracellular vesicles (EVs) into the bloodstream. These EVs are small bits of the tumor that float around in the blood and can carry important information about the cancer, like how it behaves or spreads. The researchers isolated these EVs from the blood of dogs with brain tumors to study them further. They also looked at how these tumor-derived EVs can affect different species, not just the dog itself, which is referred to as cross-species tropism. In simpler terms, the study investigates whether the particles released by the tumor can also influence other species besides just the dog. By studying these tumor-derived particles in dogs, the researchers hope to understand better how brain tumors spread and interact with other species, which could help develop new ways to detect or treat these tumors in dogs and potentially in other animals or humans.

Vincenti, S., Villa, A., de Mitri, Z., Maiolini, A., Franzé, S., Schweizer, D., Oevermann, A. and Ciana, P. (2024), Isolation of Tumour-Derived Extracellular Vesicles From the Plasma of Dogs Affected by Intracranial Tumours Showing Heterologous and Cross-Species Tropism: A Pilot Study. Vet Comp Oncol, 22: 621-628. https://doi.org/10.1111/vco.13016

Study of Feline Hodgkin-Like Lymphoma with Reed-Sternberg Cells

This study by Laura Marconato et al. from University of Bologna (Alma Mater Studiorum – Università di Bologna) , Italy, focuses on a rare type of cancer called Hodgkin-like lymphoma in cats. Lymphoma is a cancer of the lymphatic system, which is part of the immune system. In this research, the scientists specifically looked at lymphoma in cats that have Reed-Sternberg cells, which are large abnormal cells often found in Hodgkin’s lymphoma in humans. The team used different techniques to examine the cancer’s features: Histologic: Studying the tissue under a microscope to see how the cancer looks. Phenotypic: Looking at the physical characteristics of the cancer cells. Molecular: Analyzing the genetic and molecular makeup of the cancer cells. The study provides a detailed understanding of how feline Hodgkin-like lymphoma behaves, which is important for diagnosing and treating this rare cancer in cats. The findings could help develop better ways to treat similar lymphomas in cats and possibly in humans.

Marconato, L., Maga, I., Iussich, S., Benali, S. and Aresu, L. (2024), Histologic, Phenotypic, and Molecular Characterization of Feline Hodgkin-Like Lymphoma With Classical Reed-Sternberg Cells. Vet Comp Oncol, 22: 574-580. https://doi.org/10.1111/vco.13007

Immune System Changes in Canine Bladder Cancer Driven by the COX-Prostanoid Pathway

This research, led by Eto from Universität Tokio , Japan, focuses on urothelial carcinoma in dogs. The team investigated how the tumor interacts with the immune system within its environment, known as the tumor immune microenvironment. They specifically looked at the role of the COX-prostanoid cascade, a series of biological processes involving enzymes and molecules that can influence inflammation and immune responses. The study found that this pathway creates an immunosuppressive environment, which means it helps the tumor evade the immune system, allowing cancer to grow and spread more easily. Understanding how the COX-prostanoid pathway suppresses the immune system in canine bladder cancer could lead to new treatments that target this mechanism. These therapies might enhance the immune system’s ability to fight the cancer, benefiting both dogs and potentially humans with similar cancers.

Eto, S., Kato, D., Saeki, K., Iguchi, T., Shiyu, Q., Kamoto, S., Yoshitake, R., Shinada, M., Ikeda, N., Tsuboi, M., Chambers, J., Uchida, K., Nishimura, R. and Nakagawa, T. (2024), Comprehensive Analysis of the Tumour Immune Microenvironment in Canine Urothelial Carcinoma Reveals Immunosuppressive Mechanisms Induced by the COX–Prostanoid Cascade. Vet Comp Oncol, 22: 500-512. https://doi.org/10.1111/vco.12999

How Bone Cancer Prepares to Spread in Dogs

This research, led by Mikael kerboeuf et al. from the NMBU – Norwegian University of Life Sciences , Norway, investigates how the immune system in dogs interacts with cancer cells in osteosarcoma, a type of bone cancer common in dogs that can metastasize to other parts of the body, such as the lungs. The study focuses on something called the pre-metastatic niche. This is an environment that cancer cells prepare in distant organs before they even arrive. It involves changes in the immune system and tissue that make it easier for cancer cells to settle and grow. The researchers looked at dogs with naturally occurring osteosarcoma to better understand these immune system changes. By studying the immune cells and molecules involved, they aim to uncover why and how this niche develops. Their findings could help identify ways to prevent or slow down cancer spread. The study explores how osteosarcoma “prepares the ground” for metastasis in dogs by manipulating the immune system. This knowledge could lead to new therapies to block cancer spread, benefiting both dogs and potentially humans with similar cancers.

Kerboeuf, M., Anfinsen, K.P., Koppang, E.O., Lingaas, F., Argyle, D., Teige, J., Sævik, B.K. and Moe, L. (2024), Immunological Pre-Metastatic Niche in Dogs With Naturally Occurring Osteosarcoma. Vet Comp Oncol. https://doi.org/10.1111/vco.13026