Related Experiment Video
Updated: May 15, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Proteomics and personalized PDX models identify treatment for a progressive malignancy within an actionable timeframe
Georgina D Barnabas1,2, Tariq A Bhat2,3, Verena Goebeler2,3
1Department of Pathology, University of British Columbia, Vancouver, BC, Canada.
Abstract:
Genomics has transformed the diagnostic landscape of pediatric malignancies by identifying and integrating actionable features that refine diagnosis, classification, and treatment. Yet, translating precision oncology data into effective therapies for hard-to-cure childhood, adolescent, and young adult malignancies remains a significant challenge. We present the case for combining proteomics with patient-derived xenograft models to identify personalized treatment for an adolescent with primary and metastatic spindle epithelial tumor with thymus-like elements (SETTLE). Within two weeks of biopsy, proteomics identified elevated SHMT2 as a target for therapy with the anti-depressant sertraline. Drug response was confirmed within two months using a personalized chicken chorioallantoic membrane model of the patient's SETTLE tumor. Following failure of cytotoxic chemotherapy and second-line therapy, the patient received sertraline treatment and showed decreased tumor growth rates, albeit with clinically progressive disease. We demonstrate that proteomics and fast-track xenograft models provide supportive pre-clinical data in a clinically meaningful timeframe to impact clinical practice. By this, we show that proteome-guided and functional precision oncology are feasible and valuable complements to the current genome-driven precision oncology practices.
Insights
Combining proteomics and xenograft models offers a new approach for treating rare pediatric cancers. This precision oncology strategy identified a novel therapy, showing potential for personalized treatment in challenging cases.
Area of Science:
- Oncology
- Proteomics
- Genomics
Background:
- Genomics has advanced pediatric cancer diagnosis and treatment.
- Translating precision oncology data into effective therapies for rare pediatric malignancies remains difficult.
Purpose of the Study:
- To explore combining proteomics with patient-derived xenograft models for personalized treatment of rare pediatric tumors.
- To evaluate proteome-guided and functional precision oncology as complements to genome-driven approaches.
Main Methods:
- Proteomics analysis of tumor biopsy to identify therapeutic targets.
- Utilizing patient-derived xenograft models (chicken chorioallantoic membrane) for rapid drug response testing.
- Administering targeted therapy based on proteomic findings.
Main Results:
- Proteomics identified elevated SHMT2, suggesting sertraline as a potential therapy.
- A personalized chicken chorioallantoic membrane model confirmed drug response.
- Sertraline treatment led to decreased tumor growth rates in the patient, despite clinical progression.
Conclusions:
- Proteomics and fast-track xenograft models can generate clinically relevant preclinical data rapidly.
- Proteome-guided and functional precision oncology are feasible and valuable additions to current precision oncology practices.
- This integrated approach shows promise for treating hard-to-cure pediatric malignancies.
