2026-04-13T01:05:19Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/95532024-06-06T08:41:38Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Manzano-Muñoz, Albert author Yeste Lozano, Jose author Ortega, María A. author Martín, Fernando author López, Anna author Rosell, Jordi author Castro Boix, Sandra author Serrano, Cesar author 2023-05-18T07:09:54Z 2023-05-18T07:09:54Z 2022-12-01 Cancer therapy; Predictive markers; Translational research Terapia del cáncer; Marcadores predictivos; Investigación traslacional Teràpia del càncer; Marcadors predictius; Recerca translacional 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. Ramon y Cajal Programme, Ministerio de Economia y Competitividad grant RYC-2015–18357. (J.M.). Ministerio de Ciencia, Innovación y Universidades grant RTI2018-094533-A-I00 (J.M.). CELLEX foundation (J.M., A.M.). Beca Trienal Fundación Mari Paz Jiménez Casado (J.M.). European Research Council, grant ERC-StG-DAMOC 714317 (J.R.-A.). European Research Council, H2020 EU framework FET-open BLOC 863037 (J.R.-A.). Spanish Ministry of Economy and Competitiveness, “Severo Ochoa” Program for Centers of Excellence in R&D SEV-2020-2023 (J.R.-A.). Generalitat de Catalunya. CERCA Programme 2017-SGR-1079 (J.R.-A., J.S.). Fundación Bancaria “la Caixa”- Obra Social “la Caixa” (project IBEC-La Caixa Health Ageing) (J.R.-A.). Fero Foundation (C.S.). Networking Biomedical Research Center (CIBER). CIBER is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III (RD16/0006/0012), with the support of the European Regional Development Fund (J.S.). Apoptosi Càncer - Tractament Medicina personalitzada Medicaments - Eficàcia DISEASES::Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Rheology::Microfluidics ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Precision Medicine PHENOMENA AND PROCESSES::Cell Physiological Phenomena::Cell Death::Apoptosis ENFERMEDADES::neoplasias Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::reología::microfluídica TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::medicina de precisión FENÓMENOS Y PROCESOS::fenómenos fisiológicos celulares::muerte celular::apoptosis Microfluidic-based dynamic BH3 profiling predicts anticancer treatment efficacy