High-throughput 3D engineered paediatric tumour models for precision medicine

Area of Science:

• Oncology
• Biotechnology
• Materials Science

Background:

• Precision medicine requires effective drug sensitivity profiling for personalized cancer therapy.
• Current methods for generating patient-derived tumour models for high-throughput (HTP) screening are time-consuming and often unsuccessful.
• Obtaining adequate biopsy samples for HTP screening presents a significant challenge in paediatric oncology.

Purpose of the Study:

• To develop a novel platform for creating patient-specific paediatric tumour models.
• To overcome limitations in sample acquisition and model generation for precision medicine in paediatric cancers.
• To enable rapid and accurate drug sensitivity profiling for individualised cancer treatment.

Main Methods:

• Utilized gene expression analysis of paediatric neuroblastoma and sarcoma cohorts to identify key extracellular matrix (ECM) components.
• Engineered hydrogel systems incorporating ECM-mimic peptides for 3D bioprinting.
• Created patient-specific tumouroids using patient-derived cells from xenograft models and direct patient tumour samples.

Main Results:

• Bioprinted tumouroids successfully recapitulated the genetic and phenotypic characteristics of original tumours, including tumourigenicity.
• The engineered ECM hydrogel system facilitated the creation of patient-specific tumouroids.
• High-throughput drug screening on these tumouroids identified individualised drug sensitivities.

Conclusions:

• Developed a timely and clinically relevant technology platform for precision medicine in paediatric cancers.
• The 3D bioprinting approach using engineered ECM hydrogels offers a viable alternative to traditional tumour model generation.
• This platform has the potential to transform preclinical testing and advance personalised treatment strategies for various paediatric cancers.