A preclinical assay for chemosensitivity in multiple myeloma

Area of Science:

• Oncology
• Biotechnology
• Bioengineering

Background:

• Accurate preclinical prediction of cancer drug efficacy is challenging.
• Incorporating the tumor microenvironment into preclinical models can improve physiological relevance.
• Patient-derived primary tumors are generally preferred over cell lines for xenograft models.

Purpose of the Study:

• To develop an interdisciplinary platform for studying drug response in multiple myeloma (MM).
• To utilize microfluidic technology and patient-derived elements for a more predictive preclinical assay.
• To generate quantitative data for computational models of clinical response.

Main Methods:

• Developed a microfluidic platform using 3D extracellular matrix and mesenchymal cells from the tumor microenvironment.
• Employed sequential imaging and a digital analysis algorithm to quantify cell viability.
• Integrated computational models to generate dose-exposure-response surfaces for predictive utility.

Main Results:

• Successfully predicted chemosensitivity to bortezomib and melphalan in MM cell lines and patient-derived populations.
• Demonstrated the platform's capability to investigate environment-mediated drug resistance.
• Showcased the utility of the system for exploring drug combinations.

Conclusions:

• The developed interdisciplinary preclinical assay provides quantitative data for computational models.
• This platform enhances the prediction of clinical response in multiple myeloma.
• The system serves as a valuable tool for advancing personalized oncology.