Mouse models could help oncologists decide the best treatment course for patients with difficult to treat or metastatic cancers, suggests research from the Catalonian Institute of Oncology and Bellvitge Biomedical Research Institute in Barcelona, Spain.
Over approximately 8 months, researchers carried out a study in mice that had been transplanted with human tumor cells to try to assess which would be the best treatment option for a teenage boy with a recurrent peripheral nerve sheath tumor and lung metastases.
The boy was treated with the most effective drugs given to the mice and also had surgery to remove the lung metastases and has been free of cancer for almost 4 years.
The mouse models were created to be as similar to the patient’s cancer as possible. Tumor cells from the boy’s cancer were implanted in the sciatic nerve sheath of the mice and the animals were then treated with the same initial drugs as the patient. Similar to in the patient, the tumors in the mice had a partial response to the initial therapy and then regrew. The team also modeled the boy’s lung metastases in the mice.
As described in the journal Therapeutic Advances in Medical Oncology, the oncologists tested seven possible treatment combinations of 10 cancer drugs in the mice. These were selected using knowledge from the literature and a genetic analysis of the patient’s tumor that showed it had mutations in the mutations in the MAPK1, EED, and CDK2NA/B genes.
A combination of the drugs sorafenib plus doxorubicin achieved the best reduction in tumor volume of 71% in the mice, but was associated with significant weight loss in treated animals. The boy was therefore given the drug that achieved the next best tumor reduction in the mice of 67%, but had lower toxicity — nab-paclitaxel.
In practice, the clinicians did switch to sorafenib plus doxorubicin after trying treatment with nab-paclitaxel in the patient, as the cancer progressed after 4 months. Sorafenib plus doxorubicin was more effective, but did not completely eradicate the lung metastases and so additional surgery was needed to treat the boy. However, the combination of drug treatments and surgery appeared to work and he remains cancer free almost 4 years after the treatment was completed.
Although the treatments selected according to the mouse model, were not 100% effective, the researchers believe this could be a good approach to help treat patients with difficult-to-treat cancers.
“The experience gained in this trial can help to better plan this type of murine model in real-time, and help to fill the gap between the specific genetic alterations of each tumor and the treatments of patients, allowing to select the best therapeutic options,” says Juana Fernández Rodríguez, first author on the paper.
The researchers believe that the model could be made even more accurate, by more exact condition modelling of the metastases and treatments in the mice and also more advanced genetic screening of the patient’s tumors.
“By adding RNA sequencing and methylation data to our analysis that could provide a comprehensive variety of druggable targets to be tested in these models,” conclude the authors.