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. Human Tumor–Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing. Cancers 2020, 12, 92. http://doi.org/10.3390/cancers12010092
Human tumor–derived matrix improves the predictability of head and neck cancer drug testing
|Author:||Tuomainen, Katja1,2; Al-Samadi, Ahmed1,2; Potdar, Swapnil3;|
1Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland
2Translational Immunology Research Program (TRIMM), University of Helsinki, 00014 Helsinki, Finland
3Institute for Molecular Medicine Finland (FIMM), University of Helsinki, 00290 Helsinki, Finland
4Research Programs Unit, Genome-Scale Biology Program and Medicum, Biochemistry and Developmental Biology, University of Helsinki, 00014 Helsinki, Finland
5Biostatistics Consulting, Department of Public Health, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland
6Cancer and Translational Medicine Research Unit, University of Oulu, 90014 Oulu, Finland
7Department of Otorhinolaryngology—Head and Neck Surgery, Turku University Hospital, University of Turku, 20520 Turku, Finland
8Biotech Research and Innovation Center, Department of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
9Medical Research Center, Oulu University Hospital, 90014 Oulu, Finland
10Helsinki University Hospital, 00029 Helsinki, Finland
|Online Access:||PDF Full Text (PDF, 1.7 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2020051229431
Multidisciplinary Digital Publishing Institute,
|Publish Date:|| 2020-05-12
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.
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
This research was funded by the Doctoral Programme in Clinical Research (KLTO), the Sigrid Jusélius Foundation, the Cancer Society of Finland, the Helsinki University Central Hospital research funds, and Business Finland (TUTLI).
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).