Proteomics and personalized PDX models identify treatment for a progressive malignancy within an actionable timeframe

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.