Oncology Research Using Genetically Engineered Mouse Models

Oncology research using genetically engineered mice (GEM) to express oncogenes and model cancers has grown exponentially in the past 30 years.¹ Although there are key differences in human physiology and tumors found in human patients, the ability to delete tumor suppressor genes or promote oncogene over-expression in mice allow scientists to discover new pathways and learn about biological interactions. Mouse models are being used for oncology research in the following ways:

Brain tumor development

GEM models have been found to be very similar to histopathologically and etiologically with human gliomas (tumor typically found in brain or spine). These similarities provide new insight into “genetic events that trigger tumor initiation and progression.”² GEM models have also proven useful in investigating tumor interactions, malignancy, and activity in the tumor biology microenvironment.

Early Detection

Some cancers are much more difficult to detect early on, but GEM models are allowing for more versatile and easier detection techniques. Recent oncology research has shown that “a panel of proteins…could distinguish sera among individuals with pancreatic cancer, individuals with chronic pancreatitis, and healthy controls” as well as “predict from precancer sera samples which individuals from a pre-clinical study… would develop pancreatic cancer.”¹ This predictive testing can be applied to other cancers, as testing for biomarkers are already underway for ovarian and colon cancer.

Helping cancer treatment - chemotherapy

Chemotherapy is used in almost all advanced stages of cancer, but it causes damage to healthy tissue surrounding tumors. Because GEM have controllable genetics, researchers can advance oncology research by introducing different drugs and investigating inhibition of tumor pathways. Success was shown in the treatment of neuroendocrine cancer.²

Pitfalls

One of the weaknesses of GEM models is its difficulty to control tumor initiation, leading to trouble with reproducibility, a key aspect of clinical testing.² GEM models also tend to only introduce a small number of genetic mutations, which does not reflect the complexity of human tumors. Tumors also tend to develop quickly as turning on/off genes tends to have a large effect.¹ As GEM models become more advanced and affect more genes, they will prove even more valuable and available to oncology research.

References

1. Politi K, Pao W. How Genetically Engineered Mouse Tumor Models Provide Insights Into Human Cancer. American Society of Clinical Oncology. http://jco.ascopubs.org/content/29/16/2273.full
2. Huszthy P et al. In vivo models of primary brain tumors: pitfalls and perspectives. Neuro-Oncology. http://neuro-oncology.oxfordjournals.org/content/14/8/979.full