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Jernström S, Hongisto V, Leivonen SK, et al. Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response. Breast Cancer (Dove Med Press). 2017;9:185-198doi: 10.2147/BCTT.S115600.
Jernström, S., Hongisto, V., Leivonen, S. K., Due, E. U., Tadele, D. S., Edgren, H., Kallioniemi, O., Perälä, M., Mælandsmo, G. M., & Sahlberg, K. K. (2017). Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response. Breast cancer (Dove Medical Press), 9185-198. https://doi.org/10.2147/BCTT.S115600
Jernström, Sandra, et al. "Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response." Breast cancer (Dove Medical Press) vol. 9 (2017): 185-198. doi: https://doi.org/10.2147/BCTT.S115600
Jernström S, Hongisto V, Leivonen SK, Due EU, Tadele DS, Edgren H, Kallioniemi O, Perälä M, Mælandsmo GM, Sahlberg KK. Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response. Breast Cancer (Dove Med Press). 2017 Mar 21;9:185-198. doi: 10.2147/BCTT.S115600. eCollection 2017. PMID: 28356768; PMCID: PMC5367762.
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Breast Cancer (Dove Med Press). 2017 Mar 21;9:185-198. doi: 10.2147/BCTT.S115600. eCollection 2017.

Drug-screening and genomic analyses of HER2-positive breast cancer cell lines reveal predictors for treatment response.

Breast cancer (Dove Medical Press)

Sandra Jernström, Vesa Hongisto, Suvi-Katri Leivonen, Eldri Undlien Due, Dagim Shiferaw Tadele, Henrik Edgren, Olli Kallioniemi, Merja Perälä, Gunhild Mari Mælandsmo, Kristine Kleivi Sahlberg

Affiliations

  1. Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital; KG Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
  2. Misvik Biology Oy, Turku.
  3. Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital.
  4. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki; Medisapiens, Helsinki, Finland.
  5. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki.
  6. VTT Technical Research Centre of Finland, Turku, Finland.
  7. KG Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo, Norway; Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway; Institute of Pharmacy, Faculty of Health Sciences, University of Tromsø, Tromsø.
  8. Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital; Department of Research, Vestre Viken Hospital Trust, Drammen, Norway.

PMID: 28356768 PMCID: PMC5367762 DOI: 10.2147/BCTT.S115600

Abstract

BACKGROUND: Approximately 15%-20% of all diagnosed breast cancers are characterized by amplified and overexpressed HER2 (= ErbB2). These breast cancers are aggressive and have a poor prognosis. Although improvements in treatment have been achieved after the introduction of trastuzumab and lapatinib, many patients do not benefit from these drugs. Therefore, in-depth understanding of the mechanisms behind the treatment responses is essential to find alternative therapeutic strategies.

MATERIALS AND METHODS: Thirteen HER2 positive breast cancer cell lines were screened with 22 commercially available compounds, mainly targeting proteins in the ErbB2-signaling pathway, and molecular mechanisms related to treatment sensitivity were sought. Cell viability was measured, and treatment responses between the cell lines were compared. To search for response predictors and genomic and transcriptomic profiling,

RESULTS: The cell lines were divided into three groups according to the growth-retarding effect induced by trastuzumab and lapatinib. Interestingly, two cell lines insensitive to trastuzumab (KPL4 and SUM190PT) showed sensitivity to an Akt1/2 kinase inhibitor. These cell lines had mutation in

CONCLUSION: Targeting the Akt-signaling pathway shows promise in cell lines that do not respond to trastuzumab. In addition, our results indicate that several molecular features determine the growth-retarding effects induced by the drugs, suggesting that parameters other than HER2 amplification/expression should be included as markers for therapy decisions.

Keywords: ErbB2; drug screening; gene expression; pharmacogenomics; predictors

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

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