Why are animals used
in cancer research?

As many of us are well aware, the search for treatments or a cure for cancer is one of the major health challenges that society faces today. Cancer is one of the most common causes of death (one in six deaths globally in 2020), yet it is only in the last 20 years that we have made real progress in our understanding and treatment of it – and many of these breakthroughs have used animal studies as a key part of that research.

The breakthrough breast cancer drug, Herceptin, first developed from research in rodents (see Cancer breakthroughs and discoveries), has contributed significantly to reductions in deaths. It has meant the odds of surviving cancer have vastly improved for patients – deaths from breast cancer, when adjusted for age differences, have dropped by almost half from the 1980s to 2020 and we continue to see promising progress for many other types of cancer.

Even before the most recent remarkable breakthroughs, fundamental research using animals has often prepared the necessary scientific groundwork. For instance, more than 100 years ago, it was with research in chickens that scientists first discovered tumour-inducing viruses – the Rous sarcoma virus (RSV). Eventually, Peyton Rous, at Rockefeller University, USA, jointly won the 1966 Medicine Nobel for this research, which provided the earliest insights into how viruses can cause cancer. Meanwhile, the effects of environmental carcinogens such as coal tar were first understood by testing on animals like mice and rabbits.

Since those early breakthroughs, we have been looking to animals time and time again to shed light on everything from how tumours form to how they can become resistant to drugs and other treatments. Successful human cancer therapies would not exist in the first place were it not for animal research to identify appropriate molecules or targets in the body, for example, and confirm that the medicines are safe and effective.

Today, many leading charities and research institutes around the world are dedicated to studying and treating cancer, in both the lab and the clinic, with a sizeable amount of their donations going towards the funding of animal studies.

Research involving animals is essential for us to save lives. Most cancer treatments used today wouldn’t exist without this type of work.

Cancer Research UK

Mouse receiving an injection (Credit: Martin Hogeboom/Netherlands Cancer Institute)

How are animals used in cancer research?

Animal studies are involved in many aspects of cancer research, through the whole scientific process, from research into the basic mechanisms of cancer, to the translation of these findings into the clinic for drug trials on humans.

Animals can be used to investigate how cancer begins, grows, develops and spreads. Often, animals (usually mice) will have cancer induced in them in some way, for instance through switching on cancer-causing genes (‘oncogenes’) in their body, either by using chemicals, or directly transplanting a tumour into a mouse.

Modifying the genes of an animal can also be used to predispose them to specific cancers – different strains of mice are bred for cancer research are the most commonly used to mimic human disease.

Researchers also use animals that do not naturally develop cancer. For instance, researchers at IRB Barcelona and SJD Paediatric Cancer Center Barcelona, both Spain, were able to genetically engineer fruit flies to study the rare bone cancer Ewing sarcoma, and successfully model how aspects of the disease occur in humans.

Animals can also be used in the discovery and development of cancer drugs and interventions. They can provide evidence of how healthy cells are targeted by cancer cells, for example, to allow specific treatments to be developed to counteract, or block this action.

In a 2022 study, researchers at the University of Surrey and the University of Leeds and HOX Therapeutics (all UK) and the University of Texas Health Science Center at Houston, USA, used mice and cell studies to stop the HOX genes that cause glioblastoma multiforme, one of the most aggressive forms of brain cancer.

Cancers are evolving diseases, capable of evading treatment and can also adapt to new environments in the body, that make past drugs ineffective. Researchers are therefore against the clock to find other ways to outsmart cancer, and animals are the best way to explore and test ways to improve, or repurpose, existing drugs. For instance, a Swiss study that included EARA member the University of Zurich, found that immune cells fused to antibodies could be a new and effective way to treat brain tumours in mice.

Personalised treatments for a patient’s specific cancer are also an emerging field of study. One method used is to transplant cells from cancer patients into animals (an avatar), so that they reflect that individual’s disease and its characteristics. This can then provide valuable information about how the person might respond to a particular treatment, as well as the number of doses that would have the optimum effect – something that can differ drastically from person-to-person. This is clearly an approach that would not be possible to test in the cancer patient themselves.

We desperately need new treatment avenues for these aggressive brain tumours. Targeting developmental genes like the HOX genes that are abnormally switched on in the tumour cells could be a novel and effective way to stop glioblastomas growing and becoming life-threatening.

Professor Susan Short, University of Leeds

Cancer breakthroughs and discoveries using animals

We use animal studies alongside many other experimental approaches and they are crucial in building up a complete picture of cancer biology. Our research using animals has helped drive advances in cancer treatment that are benefiting people with cancer all over the world today.

The Institute of Cancer Research, UK

Mice imaging (Credit: Martin Hogeboom/Netherlands Cancer Institute)

Kidney, lymphatic system, lungs, mouth, skin cancer

Immunotherapy is a revolutionary type of cancer treatment that makes use of the body’s own immune system to seek out and kill cancer cells. One notable type of immunotherapy, called checkpoint inhibitors, first showed encouraging results in mice with cancer, by switching off the ‘brakes’ that cancer cells usually use to evade attack by the immune system.

Checkpoint inhibitors have since been used to treat cancers affecting the lungs, kidneys, skin and lymphatic system, with the pioneers of the treatment winning the Nobel Prize in physiology and medicine in 2018. It was thanks to early studies in mice that Nobel laureates Professor James Allison and Dr Tasuku Honjo were able to understand the mechanism and effect of these ‘brake’ proteins, and identify that it could work as a highly effective cancer treatment in people.

As well as being instrumental in the development of checkpoint inhibitors, mice have also been important for optimising its treatment of other cancers, like mouth cancer, and investigating how to reduce side effects, and how to combine it with other treatments to boost its effectiveness.

Cervical and throat cancer

Mice, along with rabbits, chickens and monkeys, were all used to develop a vaccine for cervical cancer, which is more common in younger people. Infection with human papillomavirus (HPV) is the general cause of this kind of cancer (it is also responsible for the majority of cases of throat cancer), with this link first being uncovered by studying a version of the papillomavirus in rabbits.

Later research in mice, infected with HPV, laid the foundations for the development of HPV vaccines, preventing thousands of cancer cases. It also paved the way for vaccines that benefit animals too, since several species are also susceptible to these viruses (see the section below Curing cancer in animals). Professor Harald zur Hausen, at the German Cancer Research Center, Heidelberg, who discovered the causal link between HPV and cervical cancer, won a share of the 2008 Nobel Prize in Medicine for this valuable work.

Recent evidence from England has shown that cervical cancer has been reduced by 90% since the introduction of the HPV vaccine.

Chronic myeloid leukaemia (CML)

This cancer which affects the body's white blood cells, is another cancer where the treatment has been revolutionised by animal studies, though the drug imatinib. It was in mice that researchers, including those at Oregon Health & Science University, USA, found that a protein abnormality caused CML, which then led to the search for compounds that could block this process, and led to the design of imatinib. The drug resulted in 80% of newly diagnosed patients having no detectable leukaemia cells in one clinical trial, leading to its rapid approval for human use.

Breast, oesophagal and stomach cancer

Herceptin is a major treatment for breast cancer (and is also used for oesophageal and stomach cancer). It works to reduce tumours by attaching to and blocking the activity of the HER2 protein, which is involved in the rapid growth of breast cancer cells.

Animal research has been critical to each stage of the development of Herceptin, from the initial discovery of the protein HER2 (which promotes the growth of cancer cells) in rat tumours, to producing HER2-targeting antibodies in mice and hamsters, to testing its subsequent safety in mice and monkeys.

Results from human trials have shown that the drug is more effective than chemotherapy alone, and when combined with chemo can improve survival rates by more than a third – offering a critical lifeline for women with this aggressive type of cancer.

Animal research also continues to aid the evolution of Herceptin as a cancer treatment – a more recent study by EARA member the University of Zurich, Switzerland, was able to instruct tumour cells in mice to produce the drug, delivering a higher dose to the tumour than the normal method.

The latest significant advancement in breast cancer is a drug called capivasertib, that has been successfully used in HER2-negative breast cancers, where herceptin is not efficient. Capivasertib is designed to lock onto a cancer-driving protein called AKT and, by doing so, blocks the protein’s activity in cancer development.

The success of capivasertib in recent phase III clinical trials, a step before regulatory approval, would not be possible without animal research. Testing the drug on mice for efficiency and tolerability was an essential step in the development of capivasertib, before moving to clinical trials. Results from these studies led scientists to improve the drug by reducing two major side effects of the drug – blood pressure and heart problems – that posed a risk to patients. A prototype of the drug was also tested on mice and successfully inhibited human tumours engrafted on the animals.

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.

Prof. Paul Workman, at the Institute of Cancer Research, UK, greeted the drug with enthusiasm, saying: “It’s a new line of attack in cancer, it’s acting in a completely new way, slowing the development of resistance to treatment, and extending the length of time that people survive with advanced breast cancer before the cancer progresses”.

And while capivasertib is being initially developed against breast cancers, it is possible that it could work in other cancers, like prostate cancer, too.

Another important breast cancer treatment is the hormone therapy Tamoxifen, which can either increase or decrease levels of oestrogen, a hormone that can stimulate the growth of breast cancer. Early research in rats, starting in the 1950s, shed light on the effectiveness of Tamoxifen as a cancer therapy, as well as treatment dosage and duration, to completely stop the progression of the disease. Read more about the history of Tamoxifen development.

Which animals are used in cancer research?

Mice – especially genetically altered or ‘humanised’ strains – are the most common animal used in cancer research around the world. In the EU and Norway in 2020, a total of 794,550 mice were used in cancer research, either for basic studies into understanding the disease or translational research (research to understand human cancers). Mice made up around 95% of all the animals used for this purpose.

Mice possess many characteristics that make them suitable for investigating cancer – in particular, their high genetic similarity to humans and the fact that they can be easily manipulated at the genetic or cellular level.

A study by the Brain and Spine Institute at the Pitié-Salpêtrière Hospital, France, and Yale School of Medicine, USA, found in mice with glioblastoma that the brain tumours could be eradicated by enlarging a network of lymphatic vessels in the brain.

Because mice have short lifespans, this also allows for the study of cancer progression and biology at all life stages in the lab – something that is more challenging in larger animals, and especially people.

Looking to mice can provide researchers with an accurate picture of the complex interactions between tumours and their environment, allowing them to uncover ways to improve existing treatments, such as with immunotherapy (see the previous section above). Watch EARA's Q&A video (below) with cancer researcher Dr Tommaso Virgillio, of the Institute for Research in Biomedicine, in Bellinzona, Switzerland, to understand this more.

Mice

Mouse being scanned (Credit: Martin Hogeboom/NKI)

Unfortunately, non-animal methods are not able at the moment to reproduce these complex environments and interactions… For this reason, we really need to use animals.

Dr Tommaso Virgilio, Institute for Research in Biomedicine,
Bellinzona, Swtizerland

Humanised mice, which have had some human element added to them, are extremely useful in cancer studies because they better reflect what happens in the human body than a normal mouse. So-called PDX mice – which possess parts of human tumours and lack an immune system that would otherwise destroy the tumour – have been shown to be a reliable strain for replicating human cancers.

As well as medicines, lifestyle interventions (such as diet and exercise), environmental effects and more modern methods (such as personalised therapies) can also be reliably trialled in mice. For example, research at the Francis Crick Institute, in London, UK, saw that in experiments in mice and humans, air pollution could be an unexpected contributor to lung cancer.

Read more about the value that mice bring to biomedical research as a whole in this EARA feature.

Zebrafish

Zebrafish are small freshwater fish that have several unique advantages over other animals for the study of cancer. One major benefit is their transparency as embryos, making it easy to visualise cancer cells and tumours in the body, as well as track how they may spread – a particularly dangerous (and often terminal) process called metastasis.

An emerging use for zebrafish in cancer studies is as a xenograft, where cancer cells or tissue are transplanted into the animals. This can be done for a wide range of different cancers, as well as be derived from cancer patients themselves so that they are representative of what is happening in that person, to give reliable evidence of the potential effects of short-term treatments in the clinic.

As with mice, it is easy to induce zebrafish to develop cancer, something that is especially critical when it comes to investigating more severe conditions such as liver and pancreatic cancer. Usually, this is done by artificially introducing DNA, or genes that are linked to cancer, into zebrafish and the resulting tumours tend to have very similar characteristics to human cancers.

These fish are also useful for improving our background knowledge of the processes involved in cancer – research at Okinawa Institute of Science and Technology, Japan, uncovered an eye mutation in zebrafish that then underpinned new understanding of how cells grow and divide, and how this is linked to cancer and developing new therapies.

Zebrafish embryos also have important applications in ‘genetic screens’ – a large-scale test in which normal animals are compared with those that have had specific mutations introduced, to detect differences between them. This method can allow researchers to identify the genes, molecules and biological pathways that play a role in diseases like cancer and, later down the line, drug discovery.

Read more about how zebrafish contribute to biomedical research as a whole in this EARA feature.

Pigs

As a larger animal, pigs have many similarities with people, such as their organs, body structure and reproductive system, and so research findings can sometimes translate better to humans than with smaller animals like mice.

Ongoing research at the Technical University of Munich, Germany, is using genetically engineered livestock pigs that accurately reflect a range of human cancers – from pancreatic cancer to bone cancer to colorectal cancer, as well as colorectal cancer in pigs.

Though the use of pigs in cancer research and to model human disease is still a relatively new field, humanised pigs with transplanted human cancer tissue are showing promise in mimicking human cancers, in line with the rise in use of pigs in biomedical research as a whole. Some of the other cancer types that are being looked at in pigs include breast, ovarian, and skin cancer.

Read more about how pigs contribute to biomedical research as a whole in this EARA feature.

Monkeys

Monkeys – or non-human primates (NHPs) – are occasionally used in the early stages of cancer research, usually for the most aggressive and serious cancers like brain tumours. However, monkeys become absolutely vital in the 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.

Zebrafish housed in large groups. (Credit: MPI for Developmental Biology,
now MPIBiology Tübingen)

The close evolutionary similarity to humans, compared to any other animal used in research means their genetics, anatomy, hormones, and reproductive and immune systems in particular can reveal key information about how a particular cancer drug will behave in a person.

NHPs have played a pivotal role in the development of biologics used to treat cancer…

US National Academies of Sciences, Engineering and Medicine

It’s the law in the UK that all new drugs are assessed for safety before they can be tested in people and this usually requires testing in animals. This minimises the risk to cancer patients during the development of new treatments.

Cancer Research UK

Baby rhesus macaque (Credit: UAR)

Sometimes only monkeys possess the same specific biological component as humans, and so are the only suitable animal in which to assess certain drugs. 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.

Read more about how monkeys contribute to biomedical research as a whole in this EARA feature.

Dogs
Like us, dogs can also suffer from cancer. Cancer studies using dogs can serve to benefit not only canine health, but also provide a simpler way to study such a multifaceted disease in humans. The National Institutes of Health, USA, is looking to clinical trials in pet dogs with cancer to study human disease. A treatment using modified bacteria, which first worked for dogs with bone cancer, has also led to the recent approval of a clinical trial in young people.

Read more about how dogs contribute to biomedical research as a whole in this EARA feature.

Care of animals in cancer studies

Animals may be indispensable to cancer research, but their use is tightly regulated to ensure that such studies are justified – if a non-animal method could achieve the same results then that must always be used instead.

The welfare of research animals is also taken into account at every stage, for example by ensuring their housing conditions are comfortable and that certain animals, like rodents, have access to toys and bedding. Steps can also be taken to minimise pain caused during studies, such as by monitoring changes in behaviour and cancer growth of mice that can indicate when researchers should intervene to alleviate pain, and by which means.

All researchers who use animals must follow the principles of the 3Rs (replacement, reduction, refinement) and huge investment is going into developing alternative methods to complement animal research, such as growing mini tumours in the lab (‘organoids’), and using computer models and human cells to uncover cancer mechanisms and test drugs. For instance, a Swiss study, at the University of Bern, grew organoids from cells taken from lab mice with cancer to successfully test treatments for prostate cancer.

Other ways to grow cancer tissue outside of living organisms includes using stem cells – specialised cells that have the ability to turn into any other type of cell in the body. This can mean using human cell cultures, cultivated under lab conditions, which have the advantage of providing an unrestricted amount of material for experiments, although these techniques unfortunately do not fully replicate the complexities of human tissues inside the body.

As well as human cells, even cells from bacteria and yeast can be applied to the study of cancer processes, while computation, artificial intelligence (AI), mathematics and statistics are also able to shed light on how tumours develop and evolve.

Even though non-animal approaches are becoming more prevalent and advanced, they are still not at a stage to be a viable replacement for animals, and generally only capture a specific part of cancer behaviour rather than giving insight into a whole-body effect.

When it comes to cancer, triggering the disease in an animal is generally considered a procedure of moderate severity, although this varies depending on the severity of the cancer type (how quickly it spreads to other parts of the body, for instance). Because some animals will be euthanised if their cancer becomes fatal, some procedures are also classified as severe (when a death may be expected) or as a non-recovery procedure (when an animal needs to be killed as part of the ongoing study).

In the EU, there are also assessments of the severity of the experiments an animal might face so as to prevent the approval of research where the harm to the animal will outweigh any benefits, or insights, that might come from the study. These assessments will also determine when it is humane to end an experiment, by making decisions about a study as early as possible to minimise the burden of the procedures on the animal.

In the EU in 2020, for animals used in basic research, cancer studies had the fourth highest severity at 11% (44,301 animals classed as being used in the ‘severe’ category), behind research into the musculoskeletal system, nervous system and immune system. Meanwhile, for translational research (research to understand human cancers), 10% of procedures were classed as severe, amounting to 41,151 animals.

It isn’t only humans who can benefit from biomedical research using animals. Many other animal species also get cancer naturally, such as dogs, cats and horses. In fact, many of the cancer medicines approved for human use can also work in animals and are relevant to veterinary medicine.

On the other end of the scale, some animals that are remarkably resilient to cancer, such as naked mole rats, can also offer clues to protecting against the disease and developing more effective treatments for humans and animals alike. Research at the University of Cambridge, UK, found that the interactions between the system of cells and molecules in naked mole rats may be what prevents cancer from initially developing into tumours in the animals.

We want to be open and transparent about our research involving living animals, and we conduct our research in the most responsible manner, with great care for the wellbeing of our animals. A commitment to reduce, refine and replace animal experiments, wherever possible, underpins all our work.

EARA member, the Netherlands Cancer Institute

(Watch the guided tour of its Mouse Cancer Clinic).

Curing cancer in animals

Beyond results that have shown to benefit our companion animals, it is our hope to extend the therapy to human patients in the future and improve healthcare outcomes for those who have cancer – especially when they have no treatment options left.

Dr Ho Yoon Khei, NUS Medicine

In dogs, skin and bone cancer, and brain tumours tend to be the cancers that most frequently affect them. Studies in dogs therefore serve to benefit their own species, as well as humans. A vaccine for treating multiple types of cancer, which blocks the creation of a protein that usually provides blood to tumours, also worked in pet dogs suffering from bone and bladder cancer, as developed by Dutch researchers, including those at EARA member the University of Maastricht.

Meanwhile, research at Yoong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), successfully used stem cells to deliver a drug to pet dogs with cancer.