Tumor Xenografting in Mouse Models: A Necessity for Cancer Drug Development

  • Posted on October 23, 2014 by Pharma Models Blogging Team in Oncology

Pre-clinical cancer research – specifically drug development – often uses a standard procedure called tumor xenografting. This method essentially injects human cancer cell lines into mice to learn more about the mechanisms behind tumor growth and for developing effective cancer drugs, a paper published in Nature magazine explained.

Subcutaneous xenografts, however, may have some limitations, as they are unable to model tumors in their point of origin. Since the biological environment affects tumor growth and drug response, it is more useful to inject cancer cells directly into the organ of origin in immunocompromised mouse models.

The paper goes onto describe the methods for injecting tumor cell lines into the mouse brain in order to create orthotopic tumors. Due to the fact that these tumors are affecting the environment within the central nervous system, orthotopic tumor models may have more clinical importance when compared to standard subcutaneous xenografts. Studying orthotopic xenografts could be more useful for determining drug efficacy and tumor growth.

In order to stimulate progress in cancer drug creation, the pre-clinical research sector has seen a boom in patient-derived tumor xenografts injected into nude mice for pre-clinical testing, a study in Nature reported. Previous failures in developing agents within oncology research are often thought to be due to a lack of pre-clinical models that capture the same environment of tumors in human patients.

However, in recent years, many animal models have been developed that are biologically stable when considering mutations, metastasis, and drug response. As previously explained, orthotopic tumor models may be more beneficial for effective xenografting.

In the initial study mentioned, researchers injected tumor cell lines into a mouse brain. Initially, an incision was performed on the mouse’s scalp from the front to back. Both a drill and a syringe were used to graft the tumor cells lines into the mouse brain. After the procedure, the mice were monitored daily. Neurological symptoms, specifically abnormal motor function, were apparent three to six months afterward.

An interesting question posed in the oncology research sector is whether the patient-derived tumor xenograft model experiences changes, specifically genetic differences of the tumors, due to the engraftment process. Studies involving gene-expression analysis have shown that patient-derived tumor xenografting keeps most of the key genes and cellular pathway activity seen in the original tumor. This has been studied in non-small-cell lung cancer, pancreatic and colon cancer, and a variety of other types.

Mouse models have played an important role in cancer drug development, as these studies are vital before certain agents can be studied in human clinical trials. Xenografts of human tumors injected into immunocompromised mice are one of the most common animal models used within oncology research, according to a publication in The Journal of Cancer Research.

Human tumor xenografts used in immunodeficient mice are useful for studying drug response and contribute to important clinical developments. Currently, animal models are the best predictor for how cancer drugs will react in human clinical trials. As such, the cancer research sector holds xenografting within mouse models in high regard.

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Categories: Oncology

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