Cancer

Immunotherapy has transformed cancer treatment by harnessing the body’s own immune system to target cancer cells. One major class of immunotherapy, known as checkpoint inhibitors, was first shown to be effective in mice by revealing how cancer cells suppress immune responses. Animal studies enabled researchers to understand the molecular “brakes” used by tumours to evade immune attack and to identify ways to block them. This work laid the foundation for checkpoint inhibitor therapies now used to treat cancers of the lung, kidney, skin and lymphatic system. The pioneers of this approach were awarded the Nobel Prize in Physiology or Medicine in 2018. 
Animal research continues to play a crucial role in improving immunotherapy and understanding why it works well for some patients but not others. A recent UK study, at the Wellcome Sanger Institute, identified two genes that influence how tumours respond to immunotherapy. By combining cancer cells from patients with cells from their own immune system and testing the findings in genetically modified mice, researchers showed that tumours lacking these genes were more vulnerable to immune attack. In these mice, tumours grew more slowly and were more likely to regress when treated with immunotherapy. Data from patients supported these findings, suggesting that such genes could be used as predictors of which patients are most likely to benefit from treatment. 
In pancreatic cancer, one of the most difficult cancers to treat, decades of animal research paved the way for a new clinical trial in the UK combining an immunotherapy drug, pembrolizumab, with the targeted therapy olaparib. Pembrolizumab was first studied in humanised mice, where it was shown to help the immune system recognise and attack cancer cells, while olaparib was originally tested in mice to demonstrate how it prevents cancer cells from repairing DNA damage. Together, these approaches are now being tested in patients whose tumours carry specific genetic changes, aiming to improve outcomes while reducing unnecessary side effects. 

EARA member Uppsala University has shown that a new antibody treatment in mice combining multiple immune-activating functions can both slow tumour growth and, at higher doses, prevent cancer from developing altogether. By precisely targeting cancer-specific gene alterations and amplifying the activity of specific immune cells, this approach is used to test complex, immune-based therapies before they are considered for use in people.  

Cervical cancer remains one of the leading causes of cancer-related deaths among women worldwide. This type of cancer is most commonly caused by infection with the human papillomavirus (HPV), a widespread group of viruses with more than 100 different types, around 30 of which are sexually transmitted. Although HPV infection is very common, only a small proportion of infected people develop cancer.  Understanding why some infections progress while most do not is a key challenge in prevention and research. 

Animal research played a decisive role in uncovering the link between HPV and cancer. Research using the cottontail rabbit papillomavirus (CRPV), the first laboratory animal of cancer caused by a mammalian virus, showed how benign papilloma could progress into malignant tumours over time. On the other hand, research in cattle showed that bovine papillomavirus could lead to cancer only under certain conditions, such as in animals exposed to additional environmental risk factors. These findings helped scientists understand that HPV infection alone is often not sufficient to cause cervical cancer, and that factors such as immune function, genetics and lifestyle can influence disease progression in humans. 
Subsequent work in animals infected with HPV provided key insights that led to the development of effective vaccines, preventing thousands of cancer cases. Studies in rabbits, dogs and cattle demonstrated that immunisation could prevent infection and stop the development of papilloma and cancer. Later testing in monkeys showed that HPV vaccines triggered strong immune responses, supporting their safety before use in people. 

Animal research played a decisive role in transforming chronic myeloid leukaemia (CML) from a fatal disease into a manageable condition. Studies in mice at Oregon Health & Science University Cancer Institute revealed that a specific protein abnormality drives the disease, leading to the development of the targeted drug imatinib. Clinical trials showed that the drug eliminated detectable leukaemia cells in 80% of newly diagnosed patients, resulting in its rapid approval for use in people. 

Many blood cancer patients rely on stem cell transplants to replace damaged blood-forming cells, but this approach depends on finding a closely matched donor. In a recent study in mice, cord blood stem cells expanded using a new treatment (Zemcelpro) successfully migrated to the bone marrow and produced healthy human blood cells. These findings supported subsequent clinical studies in adults with blood cancers, where most patients showed early recovery of white blood cells and platelets. Based on this evidence, European regulatory experts have recommended the treatment for patients with no matching donors.

Animal research has also contributed to understand why some blood cancers develop in the first place. By studying, in mice, genes that control how genes are switched on or off, researchers at EARA member Max Planck Institute of Immunobiology and Epigenetics found that early-life differences could shape whether cancers are more likely to arise later as blood cancers or solid tumours. These findings open new avenues for identifying cancer risk earlier in life and for developing preventive strategies. 

Leukaemia is the most common cancer in children under 15. Studies in children have shown that those with acute lymphoblastic leukaemia (ALL) often have a less diverse microbiome - the natural community of microorganisms in the body. Researchers from the Institute of Cancer Research are now using mice to investigate how microbiome diversity influences immune development and whether strengthening immune responses early in life could reduce the risk of ALL.

Dogs also develop leukaemia and other blood cancers naturally, and these diseases often resemble the human condition in how they progress and respond to treatment. Because dogs share important genetic, biological and environmental similarities with people, studying cancer in veterinary patients has helped researchers better understand tumour behaviour and improve therapies that benefit both species. For example, dogs naturally develop a form of lymphoma that closely mirrors human non-Hodgkin’s lymphoma. Research and clinical experience in dogs contributed to refining the CHOP chemotherapy combination. Today, CHOP, and its human variant R-CHOP, remain key therapies for lymphoma in both humans and veterinary medicine. 

Breast cancer was once one of the deadliest cancers affecting women, but advances in screening and the development of new therapies have dramatically improved survival over the past decades, and animal research has underpinned the development of many of the most effective breast cancer treatments used today. 

One of the best-known examples is Herceptin, a targeted therapy for HER2-positive breast cancer. Studies in rats, mice, hamsters and monkeys were essential to identify the HER2 protein, develop antibodies that block its activity, and assess safety before the drug entered clinical trials. Herceptin has improved survival rates by more than a third for patients with this aggressive form of the disease. Research conducted at EARA member University of Zurich made tumour cells in mice to produce the Herceptin, delivering a higher dose to the tumour than the normal method.  

Animal research was also central to the development of capivasertib, a drug designed to treat HER2-negative breast cancers, where Herceptin is not efficient. A prototype of the drug was tested on mice and successfully inhibited human tumours engrafted on the animals. Also, research in mice allowed researchers to optimise the drug’s effectiveness and reduce serious side effects before it progressed successfully through phase III clinical trials. In clinical trials, capivasertib, in combination with the drug fulvestrant, has delayed the progression of advanced breast cancers, and in almost a third of the cases shrunk the tumours of patients. 

Another important breast cancer treatment, Tamoxifen, blocks the action of oestrogen in breast cancers that grow due to hormone signals. Early studies in rats dating back to the 1950s, discovered the effectiveness of Tamoxifen as a cancer therapy and established effective dosing and long-term treatment strategies. Ongoing research in mice, at Berlin Institute of Health, continues to improve the safety of Tamoxifen by clarifying how it can, in rare cases, increase the risk of tumours in the uterus, allowing doctors to better balance risks and benefits for patients.

In addition, research in female mice has revealed that the phase of the menstrual cycle can influence how well chemotherapy works against breast cancer. The research revealed that cancer treatments can be more effective during specific phases of the menstrual cycle, potentially due to changes in immune activity and blood flow in breast tissue. This work has prompted further clinical research to determine whether timing chemotherapy according to hormonal changes could improve outcomes for women with breast cancer. 

One of the main challenges in hormone-responsive breast cancer is that treatments can stop working over time, forcing patients to move to more intensive therapies. Researchers from EARA members the Netherlands Cancer Institute (NKI) and VIB Institute for Cancer Biology discovered that corticosteroids, widely used anti-inflammatory drugs, can prolong the effectiveness of hormone therapy in breast cancer. Based on this work, a phase II clinical trial will test dexamethasone alongside hormone therapy in patients whose breast cancer has become resistant to treatment. 

Zebrafish offer unique advantages in cancer research, particularly because their transparent embryos make it easier to visualise cancer cells and tumours in living animals, as well as track how they may spread. Cancer cells from patients can be transplanted into zebrafish to rapidly assess how tumours respond to different treatments and their toxicity. 

By artificially introducing genes linked to cancer into zebrafish, these animals can develop tumours that have very similar characteristics to human cancers. 

Zebrafish embryos are also widely used in genetic screens. These large-scale tests in which normal animals are compared with those that have had specific mutations introduced, to detect differences between them, allowing researchers to identify genes, molecules and pathways involved in cancer, thus supporting drug discovery. 

However, zebrafish cannot model every aspect of cancer seen in mammals. Some organs commonly affected by cancers, such as the lung, breast and prostate, are not present in zebrafish, limiting how certain tumour types can be studied. In addition, young zebrafish do not yet have a fully developed adaptive immune system, which restricts their use for studying complex interactions between tumours and the immune system. Their lower body temperature can also influence how transplanted human tumour cells behave. For questions requiring full immune responses, organ-specific cancer models or long-term disease progression, researchers therefore rely on complementary mammalian models, such as mice.

More about the role of zebrafish in biomedical research can be found here.  

Mice are the most widely used animals in cancer research due to their genetic similarity to humans and the ease with which their genes can be modified. Their short lifespan allows researchers to study cancer development, progression and treatment effects across the entire life course – something that is more challenging in larger animals and people. 

Specialised types of mice, including humanised mice and mice implanted with tumours taken directly from patients, can more closely reflect how cancers behave in patients. These animals are particularly valuable for studying interactions between tumours and the immune system, testing personalised therapies and understanding how environmental factors such as air pollution can influence tumour growth. 

More about the role of mice in biomedical research can be found here.  

Dogs naturally develop many of the same cancers seen in people, including lymphoma and leukaemia, osteosarcoma, bladder cancer and brain tumours. Cancer is also a significant health issue in companion animals, with around one in four dogs developing the disease during their lifetime. Unlike laboratory animals in which tumours are intentionally induced, these cancers arise spontaneously in pet dogs and progress in ways that closely resemble human disease. 

Because canine cancers share features and treatment responses with human cancers, studying them can generate insights that benefit both veterinarian and human medicine. Clinical trials in pet dogs are designed first and foremost to support the participating animals, offering access to advanced diagnostics and emerging therapies that may improve survival and quality of life. At the same time, researchers gain valuable information about how treatments perform in naturally occurring disease. Ongoing veterinary trials are now evaluating advanced immunotherapies and drug-delivery methods that target tumours directly, such as cytokine treatments designed to stay anchored at the tumour, tested in dogs with melanoma.  

This approach, known as comparative oncology, enables a two-way exchange of knowledge. Findings from veterinary studies inform human cancer research, while advances in human oncology improve care for companion animals. For example, clinical trials in dogs with osteosarcoma, an aggressive bone cancer seen in children and large dog breeds, helped advance immunotherapies targeting the HER2 protein, improving survival in canine patients and supporting ongoing trials in children. Similarly, studies of naturally occurring canine lymphoma, which closely mirrors human non-Hodgkin’s lymphoma, have helped refine chemotherapy and immunotherapy approaches used in both species. Several other cancer treatments have progressed from canine clinical studies to human trials. 

“With today’s data, we believe we are taking the first steps towards this given that our comparative oncology approach, as a result of the 96% genetic homology between human and canine osteosarcoma, leads us to believe there is significant potential for this canine data to translate into humans in the treatment of frontline and primary metastatic osteosarcoma,” said Paul Romness, OS Therapies. 

More about the role of dogs in biomedical research can be found here. 

Pigs share many anatomical and physiological similarities with humans, such as their organs, body structure and size. This makes them especially valuable when researchers need to test medical procedures, imaging technologies or therapies in conditions that closely match how cancer is treated in patients - something that smaller animals such as mice cannot always model.

For example, pigs are widely used to develop and refine minimally invasive cancer treatments, particularly for liver and lung tumours. Their organ size and anatomy allow researchers to trial techniques and advanced imaging-guided procedures using the same equipment and approaches used in hospitals. 

Genetically altered pigs also allow researchers to study tumour initiation, progression and immune responses. The Oncopig model carries human-relevant mutations in genes that are commonly associated with pancreatic, colorectal and other cancers. Thus, tumour induction in Oncopigs reproduces the immune responses seen in humans, including alterations in cells from the immune system, allowing evaluation of immunotherapies in a more accurate manner. 

Pigs with mutations in the APC gene develop polyps in the colon and rectum that have the same genetic signature of human adenocarcinoma. In mice, APC mutations alone often produce polyps mainly in the small intestine, requiring additional modifications to mimic human disease. Oncopigs can be engineered to develop tumours in the pancreatic ducts with the same features as human pancreatic cancer. Their size also allows laparoscopic procedures, advanced CT imaging and long-term monitoring. 

More about the role of pigs in biomedical research can be found here. 

Monkeys are mainly used in in cancer research during later stages of drug development to assess any new, or experimental, cancer drugs (that it is hoped may go on to human trials and, eventually, regulatory approval) to check for any unforeseen, or harmful effects they may have. Before reaching primate studies, these drugs are thoroughly tested in other models, such as mice or rats, to gather as much information as possible about efficacy, dosing and potential toxicity. Only after this preliminary data is collected do non-human primates provide critical insights that other models cannot. 

Their close evolutionary similarity to humans means that NHP genetics, anatomy, hormones and reproductive and immune systems can reveal key information about how a particular cancer drug will behave in a person. This makes them essential for assessing the safety of new cancer treatments, particularly biologics, such as antibodies, after preliminary studies in rodents or other models have provided initial data. There are additional strict regulations and ethical standards that are applied for research in monkeys to ensure they are only used when there is no viable alternative. 

More about the role of monkeys in biomedical research can be found here.