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Published on: July 15, 2015
OncoFlow: A multiplexed microfluidic platform for personalized drug sensitivity assessment
Matan Krasner1, Efrat Barbiro-Michaely1, Ulrike Bening Abu-Shach2
1The Mina & Everard Goodman Faculty of Life Sciences and the Institute for Nanotechnology and Advanced Materials, Bar Ilan University, Ramat-Gan, Israel.
Abstract:
While biomarker-guided treatments and NGS-based approaches are refining precision medicine, they are not universally applicable. The gap between the genomic characterization of tumors and their functional behavior is becoming increasingly evident. There is an escalating demand for functional assays that can customize cancer treatments for individual patients and bridge this gap. We have developed OncoFlow, an integrated microfluidic platform that automates viability assays. This platform customizes treatment options by assessing the functional responses of a patient's tumor cells to a specific drug panel. This study specifically addressed non-small cell lung adenocarcinoma (NSCLC) in patients presenting pleural effusion. We used the NCI-H2228 adenocarcinoma cell line, which harbors the EML4-ALK fusion oncogene, to develop and fine-tune the viability assay. Cells cultivated in microfluidic chambers were treated with various concentrations of the tyrosine kinase inhibitors alectinib and crizotinib, and the cytotoxic effects were measured. The results were consistent with those from conventional cell culture methods, thereby validating the assay's reliability. Next, pleural effusion samples from six NSCLC patients, four of them harboring the EML4-ALK rearrangement were tested with alectinib and crizotinib using the OncoFlow system. Monitoring and analysis of cell viability showed varied sensitivities to crizotinib, while all samples exhibited resistance to alectinib. These findings underscore OncoFlow's potential to enhance physician decision-making and customize treatment plans, ultimately improving patient outcomes.
Insights
OncoFlow, a microfluidic platform, assesses patient tumor cell drug response for personalized non-small cell lung adenocarcinoma (NSCLC) treatment. It revealed varied sensitivities to crizotinib and resistance to alectinib in NSCLC pleural effusion samples.
Area of Science:
- Oncology
- Biotechnology
- Microfluidics
Background:
- Precision medicine advances like biomarker-guided treatments and next-generation sequencing (NGS) have limitations.
- A gap exists between tumor genomic characterization and functional behavior, necessitating functional assays.
- There is a growing need for personalized cancer treatment strategies based on individual patient responses.
Purpose of the Study:
- To develop and validate OncoFlow, an automated microfluidic platform for functional viability assays.
- To assess the efficacy of OncoFlow in customizing treatment options for non-small cell lung adenocarcinoma (NSCLC) patients.
- To evaluate patient tumor cell sensitivity to specific tyrosine kinase inhibitors using the OncoFlow system.
Main Methods:
- Development of OncoFlow, an integrated microfluidic platform for automated viability assays.
- Validation of the assay using the NCI-H2228 adenocarcinoma cell line (EML4-ALK fusion) with alectinib and crizotinib.
- Testing of pleural effusion samples from six NSCLC patients, including four with EML4-ALK rearrangement, on the OncoFlow system.
Main Results:
- The OncoFlow assay's reliability was confirmed by its consistency with conventional cell culture methods.
- Patient-derived NSCLC cells showed varied sensitivities to crizotinib.
- All tested NSCLC patient samples exhibited resistance to alectinib.
Conclusions:
- OncoFlow effectively assesses functional drug responses in patient tumor cells.
- The platform demonstrates potential for enhancing physician decision-making in NSCLC treatment.
- OncoFlow can contribute to the customization of cancer treatment plans and improved patient outcomes.

