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

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–rele...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017272/
https://www.ncbi.nlm.nih.gov/pubmed/31905951
http://dx.doi.org/10.3390/cancers12010092
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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
author_facet 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
author_sort Tuomainen, Katja
collection PubMed
description 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.
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spelling pubmed-70172722020-02-28 Human Tumor–Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing 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 Cancers (Basel) Article 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. MDPI 2019-12-30 /pmc/articles/PMC7017272/ /pubmed/31905951 http://dx.doi.org/10.3390/cancers12010092 Text en © 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/).
spellingShingle Article
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
Human Tumor–Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing
title Human Tumor–Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing
title_full Human Tumor–Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing
title_fullStr Human Tumor–Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing
title_full_unstemmed Human Tumor–Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing
title_short Human Tumor–Derived Matrix Improves the Predictability of Head and Neck Cancer Drug Testing
title_sort human tumor–derived matrix improves the predictability of head and neck cancer drug testing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017272/
https://www.ncbi.nlm.nih.gov/pubmed/31905951
http://dx.doi.org/10.3390/cancers12010092
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