A team of researchers at St. Jude Children’s Research Hospital has created a new series of innovative models that represent different types of pediatric brain tumors. These models are called orthotopic patient-derived xenograft (O-PDX) models, and they’re used to further research on brain tumors and test novel therapies. The point of O-PDX models is that they enable researchers to observe cancer growth in mice and help to design a customized treatment for the patient. They’ve been heralded as being “the future of personalized cancer treatment.”
How are O-PDX models made?
To develop an O-PDX model, scientists must first consult with the parents of the patient and get consent. Once the parents and scientists are in agreement, a team of researchers extract cancerous cells from the patient. Then, the cells are implanted orthotopically (in the same tissue) in immunocompromised mice. The advantage of testing O-PDX models in mice is that the mouse tumors do not differ in biology from the tumors originally diagnosed in the patient. This means that a cancer therapy developed using an O-PDX model that is effective in the infected mice will likely be just as effective in a human cancer patient.
“We started out by researching medulloblastoma and needing a good model that we could use to screen for novel therapies,” said co-senior author Martine Roussel, Ph.D., St. Jude Tumor Cell Biology. “Our current database of models is the result of many years of work by our lab as well as with many collaborators in surgery, oncology, pathology and computational biology.”
A complex process
The researchers created 37 models in total, which were created from tumor samples donated by patient families. Tumor samples included pediatric medulloblastoma, ependymoma, atypical teratoid rhabdoid tumor, and embryonal tumors. The scientists then characterized the models through a complex series of methods: A combination of histopathology, whole-genome and whole-exome sequencing, RNA-sequencing, and DNA methylation analysis. The resulting product paved the way for the researchers to start work on brand-new cancer treatments–wholly based on the patient’s individual genome.
“To effectively treat childhood brain tumors, we need to have additional treatment strategies in our toolkit,” said author Frederick Boop, M.D., Pediatric Neurosurgery Division chief at St. Jude. “It takes many different scientific and medical specialties working together to create these types of models and conduct essential preclinical research that paves the way for new clinical trials.”
Using the models to advance cancer research
The researchers reported that the creation of the models led to the launch of three clinical trials, which will test new therapies for brain tumors.
The O-PDX models were also made available on an internet-based platform for doctors and scientists called St. Jude Cloud. The platform is cloud-based, meaning all the information it contains is accessible to medical professionals. The sharing of these models means researchers will be able to begin working on new cancer treatments without recreating the research already performed at St. Jude’s.
Every time we see new breakthroughs like this one, we get another step closer to defeating cancer.