Canadian researchers have developed an innovative method to quickly identify a personalized treatment for a pediatric cancer patient by cultivating their tumors in chicken eggs and analyzing their proteins. The integrated techniques were used to determine and test a potential treatment within the timeframe of a patient’s therapy.
Their technique, published in EMBO Molecular Medicine case study, highlights proteomics as a valuable complement to genomics in real-time cancer treatment. This study demonstrates that integrating proteomics with patient-derived xenograft models can enhance personalized treatment strategies, as shown in the case of an adolescent diagnosed with spindle epithelial tumor with thymus-like elements (SETTLE).
A case study in functional precision oncology
The research was conducted as part of PROFYLE (PRecision Oncology For Young peopLE), an initiative under the Canadian pediatric cancer network ACCESS (Advancing Childhood Cancer Experience, Science, and Survivorship). PROFYLE unites more than 30 research and funding organizations and over 100 investigators across Canada to improve cancer outcomes for children and young adults.
The researchers focused on a young patient whose rare pediatric cancer had proven resistant to conventional treatments. Standard chemotherapy had failed, and genomic analyses did not reveal a clear therapeutic option. In response, the team turned to proteomics, which identified SHMT2, an enzyme crucial to the tumor’s metabolism, as a potential target for therapy.
Recognizing the role of SHMT2 in the tumor’s metabolic processes, researchers proposed an unconventional treatment: sertraline, a commonly used antidepressant known to inhibit SHMT2. Unlike traditional chemotherapy drugs, sertraline disrupts the tumor’s ability to access key energy sources, potentially slowing its progression.
To evaluate the effectiveness of sertraline against the patient’s tumor, the team employed a novel xenograft model using chicken embryos. The team grew a small piece of the patient’s tumor on a chicken egg, which served as an avatar host for the tumor. Growing an identical tumor outside the patient allowed researchers to test drug responses within weeks—far faster than traditional methods that rely on rodent models.
Encouraging outcomes and future directions
The results of the study were promising but not curative. After the patient began sertraline treatment, tumor growth rates slowed, although the disease continued to progress.
Key findings include:
- Proteomic analysis identified SHMT2 as a critical metabolic target in the patient’s tumor.
- Chicken egg xenograft models enabled rapid drug response testing within weeks.
- Sertraline, an FDA-approved antidepressant, demonstrated anti-tumor activity in preclinical testing.
Despite its limitations, this case study demonstrates the feasibility of proteomics-guided precision medicine and rapid xenograft models in identifying actionable treatment options within a clinically meaningful timeframe.
Transforming cancer treatment through multi-omics approaches
This study contributes to a growing body of evidence supporting the integration of multi-omics approaches—combining genomics, proteomics, and functional drug testing—to refine precision oncology. The researchers believe this approach represents a paradigm shift in pediatric oncology, demonstrating how integrating proteomics and patient-derived xenograft models can accelerate personalized treatment strategies for rare and difficult-to-treat cancers.
While this study was limited to a single patient, the researchers now aim to expand their approach to more children with hard-to-treat cancers across Canada, potentially establishing a new standard for integrating proteomics into pediatric oncology.
