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

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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

Title: Human Tumor-Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing
Author: Tuomainen, Katja; Al-Samadi, Ahmed; Potdar, Swapnil; Turunen, Laura; Turunen, Minna; Karhemo, Piia-Riitta; Bergman, Paula; Risteli, Maija; Åström, Pirjo; Tiikkaja, Riia; Grenman, Reidar; Wennerberg, Krister; Monni, Outi; Salo, Tuula
Contributor organization: HUS Head and Neck Center
Department of Oral and Maxillofacial Diseases
Clinicum
Faculty of Medicine
University of Helsinki
TRIMM - Translational Immunology Research Program
Research Programs Unit
Institute for Molecular Medicine Finland
Genome-Scale Biology (GSB) Research Program
Department of Biochemistry and Developmental Biology
Department of Public Health
Helsinki University Hospital Area
Krister Wennerberg / Principal Investigator
Department of Oncology
Medicum
HUSLAB
Date: 2020-01
Language: eng
Number of pages: 15
Belongs to series: Cancers
ISSN: 2072-6694
DOI: https://doi.org/10.3390/cancers12010092
URI: http://hdl.handle.net/10138/314700
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.
Subject: head and neck cancer
drug screening
human tumor microenvironment
clinical trials
in vitro 3D
SQUAMOUS-CELL CARCINOMA
PHASE-II TRIAL
RECURRENT
PATHWAY
INHIBITOR
CETUXIMAB
SYSTEMS
ZD1839
EGFR
3122 Cancers
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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