Cancer is a highly researched disease. Thousands of mouse studies are published every year, and cancer patients are inundated with headlines claiming breakthroughs and promising discoveries. To understand the context of these reported data, you need to know the mouse model used in the experiments. This information is often not included in main stream publications, but it is typically included in the abstract of the original paper.
As a quick guide for patients, there are three basic mouse models in use. There is tremendous variation within each model and it can be very hard to understand the details; however, each of the three models has consistent strengths and weaknesses.
XENOGRAFTS: In this model, human cancer cells are injected into a mouse, usually just under the skin. Most cancer experiments are performed in xenograft mice. They are considered the least predictive of human clinical performance.
- Xenografts allow researchers to examine how a specific cancer cell populations responds to an experimental therapy.
- They provide a much better model than experiments performed in a petri dish, where cancer drugs are not metabolized as they would be in a live animal and cancer cells are not exposed to other cell types, tissues, and biological functions.
- Scientists can see the tumor grow, which allows them to easily measure data such as tumor volume and take biopsies of tumor tissue to determine how well (or not) an experimental therapy is working.
- These mice must have significantly compromised immune systems. If they didn’t, their immune systems would destroy the injected cancer cells.
- xenograft tumors are not comparable to human tumors in many ways. Their blood vessel architecture is different which changes how much drug gets into the tumor and they are unrealistically large – a comparable human tumor would fit into a wheel barrow.
- Tumors in these mice are not in the same organ/tissues as they would be in a human patient. A breast cancer tumor grown on the back of a mouse is under significantly different hormonal influences than one growing in breast tissue.
ORTHOTOPIC XENOGRAFTS: Similar to xenografts, human cells are injected into these mice; however, the cancer cells are placed in the relevant organ or tissue. For instance, a scientist studying pancreatic cancer would inject human cancer cells directly into the pancreas of the mice. This allows a tumor to grow in an environment that is similar to a human patient. The other weaknesses of xenografts apply to these mice. Additionally, tumors are not as easily measured and manipulated since they may not appear on the surface of the mouse.
GENETICALLY ENGINEERED: Genetically engineered mouse models (GEMMS) are relatively new. In these models, scientists use genetic manipulation to create a strain of mice that “naturally” develops tumors with similar mutations to human tumors. For instance, Pancreatic cancer GEMMS have mutations in their KRAS gene (and others) similar to what scientist observe in human pancreatic adenocarcinoma patients. Some, but not all, of the mice born with this mutation will develop pancreatic tumors.
Scientist use these mouse models to examine how experimental therapies work on known cancer-causing pathways, and to investigate elements of the tumor micro-environment that more closely approximate human tumors than can be achieved in xenograft models. In general, researcher view data from GEMMs as more predictive of human clinical performance than data coming from xenografts.
- Because these mice develop tumors that are “natural” rather than injected, the tumors tend to have more realistic blood vessel architecture and size. These models can produce tumors that are structurally much more realistic and predictive than xenografts. However, care must be take to make sure this is the case by directly comparing human and GEMM tumor morphology.
- GEMMs have functioning immune systems, which makes them far better for studying the latest immunotherapies.
- GEMMs can be significantly better predictors of human clinical performance; however this depends on the model, the experiment and the cancer being investigated.
- These models may not accurately reflect all of the genetic components of a human tumor population and there may be elements of mouse biology that positively or negatively influence experimental results in ways that are difficult to predict.
- They are much more costly and more time consuming than xenograft mice. Each mouse model can take many years to perfect and not every mouse develops cancer.