High-throughput screening in colorectal cancer tissue-originated spheroids

Area of Science:

• Oncology
• Drug Discovery
• Biotechnology

Background:

• Patient-derived cancer organoids reflect clinical heterogeneity but are limited for high-throughput screening due to expansion time and cost.
• Existing methods face challenges in scaling organoid cultures for comprehensive drug testing across multiple patients.

Purpose of the Study:

• To develop and validate an advanced system for high-throughput drug screening using cancer tissue-originated spheroids (CTOS).
• To enable efficient drug evaluation on a large scale using patient-derived cancer models.

Main Methods:

• The study applied the CTOS method on an ex vivo platform derived from xenograft tumors.
• Automated systems were used for handling CTOS and reagents, with a reference panel of multiple CTOS lines tested against 2427 drugs.
• CTOS were passaged through xenograft tumors to expand their numbers while maintaining genomic and morphological stability.

Main Results:

• Xenograft tumor generation efficiently expanded CTOS numbers with minimal changes in morphology and genomic status.
• The CTOS reference panel demonstrated diverse sensitivities to hit compounds, validating the system's utility.
• The system facilitated high-throughput screening of 2427 drugs.

Conclusions:

• The developed CTOS-based system offers a practical solution for high-throughput drug screening of patient-derived cancer models.
• This platform is valuable for investigating highly heterogeneous diseases like colorectal cancer by assessing diverse drug sensitivities.
• The method overcomes limitations of traditional organoid cultures for large-scale drug discovery.