Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response

Petreus et al. describe a platform combining 3D tumour-on-chip technology and pump driven microfluidics to study drug effects at physiological exposures preclinically. They test colorectal cancer spheroids with combinations of two drugs and show that it can successfully predict efficacy in vivo, thereby providing a valuable tool for drug response and pharmacodynamic assessment and reducing the need for animal studies. Microphysiological in vitro systems are platforms for preclinical evaluation of drug effects and significant advances have been made in recent years. However, existing microfluidic devices are not yet able to deliver compounds to cell models in a way that reproduces the real physiological drug exposure. Here, we introduce a novel tumour-on-chip microfluidic system that mimics the pharmacokinetic profile of compounds on 3D tumour spheroids to evaluate their response to the treatments. We used this platform to test the response of SW620 colorectal cancer spheroids to irinotecan (SN38) alone and in combination with the ATM inhibitor AZD0156, using concentrations mimicking mouse plasma exposure profiles of both agents. We explored spheroid volume and viability as a measure of cancer cells response and changes in mechanistically relevant pharmacodynamic biomarkers (gamma H2AX, cleaved-caspase 3 and Ki67). We demonstrate here that our microfluidic tumour-on-chip platform can successfully predict the efficacy from in vivo studies and therefore represents an innovative tool to guide drug dose and schedules for optimal efficacy and pharmacodynamic assessment, while reducing the need for animal studies.

Automated summary

Petreus et al. introduce a novel tumour-on-chip microfluidic system that mimics pharmacokinetic profiles of compounds on 3D tumour spheroids to evaluate their response to treatments, successfully predicting efficacy from in vivo studies and guiding drug dose and schedules for optimal efficacy while reducing the need for animal studies.