2. Academic Validation
  3. Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy

Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy

  • NPJ Precis Oncol. 2022 Dec 1;6(1):90. doi: 10.1038/s41698-022-00333-0.
Albert Manzano-Muñoz 1,  José Yeste 2,  María A Ortega 2 3,  Fernando Martín 1 4,  Anna López 2,  Jordi Rosell 5,  Sandra Castro 6,  César Serrano 5 7,  Josep Samitier 1 4 8,  Javier Ramón-Azcón # 2 9,  Joan Montero # 10 11 12
Affiliations

Affiliations

  • 1 Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • 2 Biosensors for Bioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • 3 Vitala Technologies, Barcelona, Spain.
  • 4 Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
  • 5 Sarcoma Translational Research Program, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitario Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
  • 6 Surgical Oncology Division, Vall d'Hebron University Hospital, Barcelona, Spain.
  • 7 Department of Medical Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
  • 8 Department of Electronics and Biomedical Engineering, Faculty of Physics, University of Barcelona, Barcelona, Spain.
  • 9 Institució Catalana de Reserca i Estudis Avançats (ICREA), Passeig de Lluís Companys, 23, E08010, Barcelona, Spain.
  • 10 Nanobioengineering Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. jmontero@ub.edu.
  • 11 Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain. jmontero@ub.edu.
  • 12 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universitat de Barcelona, Casanova 143, Barcelona, 08036, Spain. jmontero@ub.edu.
  • # Contributed equally.
PMID: 36456699 DOI: 10.1038/s41698-022-00333-0
Abstract

Precision medicine is starting to incorporate functional assays to evaluate Anticancer agents on patient-isolated tissues or cells to select for the most effective. Among these new technologies, dynamic BH3 profiling (DBP) has emerged and extensively been used to predict treatment efficacy in different types of Cancer. DBP uses synthetic BH3 peptides to measure early apoptotic events ('priming') and anticipate therapy-induced cell death leading to tumor elimination. This predictive functional assay presents multiple advantages but a critical limitation: the cell number requirement, that limits drug screening on patient samples, especially in solid tumors. To solve this problem, we developed an innovative microfluidic-based DBP (µDBP) device that overcomes tissue limitations on primary samples. We used microfluidic chips to generate a gradient of Bim BH3 peptide, compared it with the standard flow cytometry based DBP, and tested different Anticancer treatments. We first examined this new technology's predictive capacity using gastrointestinal stromal tumor (GIST) cell lines, by comparing imatinib sensitive and resistant cells, and we could detect differences in apoptotic priming and anticipate cytotoxicity. We then validated µDBP on a refractory GIST patient sample and identified that the combination of dactolisib and venetoclax increased apoptotic priming. In summary, this new technology could represent an important advance for precision medicine by providing a fast, easy-to-use and scalable microfluidic device to perform DBP in situ as a routine assay to identify the best treatment for Cancer patients.

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