Human Tumor-Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing

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dc.contributor.author Tuomainen, Katja
dc.contributor.author Al-Samadi, Ahmed
dc.contributor.author Potdar, Swapnil
dc.contributor.author Turunen, Laura
dc.contributor.author Turunen, Minna
dc.contributor.author Karhemo, Piia-Riitta
dc.contributor.author Bergman, Paula
dc.contributor.author Risteli, Maija
dc.contributor.author Åström, Pirjo
dc.contributor.author Tiikkaja, Riia
dc.contributor.author Grenman, Reidar
dc.contributor.author Wennerberg, Krister
dc.contributor.author Monni, Outi
dc.contributor.author Salo, Tuula
dc.date.accessioned 2020-05-06T10:36:01Z
dc.date.available 2020-05-06T10:36:01Z
dc.date.issued 2020-01
dc.identifier.citation Tuomainen , K , Al-Samadi , A , Potdar , S , Turunen , L , Turunen , M , Karhemo , P-R , Bergman , P , Risteli , M , Åström , P , Tiikkaja , R , Grenman , R , Wennerberg , K , Monni , O & Salo , T 2020 , ' Human Tumor-Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing ' , Cancers , vol. 12 , no. 1 , 92 . https://doi.org/10.3390/cancers12010092
dc.identifier.other PURE: 136650302
dc.identifier.other PURE UUID: 5c50b17e-1577-41cb-9da2-d0ddf2dc4d22
dc.identifier.other WOS: 000516826700092
dc.identifier.other ORCID: /0000-0001-6039-0088/work/73631193
dc.identifier.other ORCID: /0000-0003-3330-1670/work/73634106
dc.identifier.other ORCID: /0000-0002-2778-6918/work/73634231
dc.identifier.other ORCID: /0000-0003-4672-2554/work/73634502
dc.identifier.uri http://hdl.handle.net/10138/314700
dc.description.abstract In vitro cancer drug testing carries a low predictive value. We developed the human leiomyoma-derived matrix "Myogel" to better mimic the human tumor microenvironment (TME). We hypothesized that Myogel could provide an appropriate microenvironment for cancer cells, thereby allowing more in vivo-relevant drug testing. We screened 19 anticancer compounds, targeting the epidermal growth factor receptor (EGFR), MEK, and PI3K/mTOR on 12 head and neck squamous cell carcinoma (HNSCC) cell lines cultured on plastic, mouse sarcoma-derived Matrigel (MSDM), and Myogel. We applied a high-throughput drug screening assay under five different culturing conditions: cells in two-dimensional (2D) plastic wells and on top or embedded in Matrigel or Myogel. We then compared the efficacy of the anticancer compounds to the response rates of 19 HNSCC monotherapy clinical trials. Cancer cells on top of Myogel responded less to EGFR and MEK inhibitors compared to cells cultured on plastic or Matrigel. However, we found a similar response to the PI3K/mTOR inhibitors under all culturing conditions. Cells grown on Myogel more closely resembled the response rates reported in EGFR-inhibitor monotherapy clinical trials. Our findings suggest that a human tumor matrix improves the predictability of in vitro anticancer drug testing compared to current 2D and MSDM methods. en
dc.format.extent 15
dc.language.iso eng
dc.relation.ispartof Cancers
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject head and neck cancer
dc.subject drug screening
dc.subject human tumor microenvironment
dc.subject clinical trials
dc.subject in vitro 3D
dc.subject SQUAMOUS-CELL CARCINOMA
dc.subject PHASE-II TRIAL
dc.subject RECURRENT
dc.subject PATHWAY
dc.subject INHIBITOR
dc.subject CETUXIMAB
dc.subject SYSTEMS
dc.subject ZD1839
dc.subject EGFR
dc.subject 3122 Cancers
dc.title Human Tumor-Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing en
dc.type Article
dc.contributor.organization HUS Head and Neck Center
dc.contributor.organization Department of Oral and Maxillofacial Diseases
dc.contributor.organization Clinicum
dc.contributor.organization Faculty of Medicine
dc.contributor.organization University of Helsinki
dc.contributor.organization TRIMM - Translational Immunology Research Program
dc.contributor.organization Research Programs Unit
dc.contributor.organization Institute for Molecular Medicine Finland
dc.contributor.organization Genome-Scale Biology (GSB) Research Program
dc.contributor.organization Department of Biochemistry and Developmental Biology
dc.contributor.organization Department of Public Health
dc.contributor.organization Helsinki University Hospital Area
dc.contributor.organization Krister Wennerberg / Principal Investigator
dc.contributor.organization Department of Oncology
dc.contributor.organization Medicum
dc.contributor.organization HUSLAB
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.3390/cancers12010092
dc.relation.issn 2072-6694
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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