BackgroundWidely established targeted therapies directed at triple negative breast cancer (TNBC) are missing. Classical chemotherapy remains the systemic treatment option. Cisplatin has been tested in TNBC but bears the disadvantage of resistance development. The purpose of this study was to identify resistance mechanisms in cisplatin-resistant TNBC cell lines and select targeted therapies based on these findings.MethodsThe TNBC cell lines HCC38 and MDA-MB231 were subjected to intermittent cisplatin treatment resulting in the 3.5-fold cisplatin-resistant subclone HCC38CisR and the 2.1-fold more resistant MDA-MB231CisR. Activation of pro-survival pathways was explored by immunostaining of phospho-receptor tyrosine kinases. Targeted therapies (NVP-AEW541, lapatinib and NVP-BEZ235) against activated pathways were investigated regarding cancer cell growth and cisplatin sensitivity.ResultsIn HCC38CisR and MDA-MB231CisR, phosphorylation of epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) was observed. In HCC38CisR, treatment with NVP-AEW541 increased potency of lapatinib almost seven-fold, but both compounds could not restore cisplatin sensitivity. However, the dual phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235 acted synergistically with cisplatin in HCC38CisR and fully restored cisplatin sensitivity. Similarly, NVP-BEZ235 increased cisplatin potency in MDA-MB231CisR. Furthermore, NVP-AEW541 in combination with lapatinib restored cisplatin sensitivity in MDA-MB231CisR.ConclusionSimultaneous inhibition of EGFR and IGF1R in cisplatin-resistant TNBC cell lines was synergistic regarding inhibition of proliferation and induction of apoptosis. Co-treatment with NVP-BEZ235 or with a combination of NVP-AEW541 and lapatinib restored cisplatin sensitivity and may constitute a targeted treatment option for cisplatin-resistant TNBC.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3695-5) contains supplementary material, which is available to authorized users.

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Die Funktionsprüfung des Steuerungscodes eines Leitsystems ist integraler Bestandteil der Werksabnahme (factory acceptance test, FAT) einer Automatisierungslösung; sie wird heute weitestgehend manuell durchgeführt. Dies führt dazu, dass die Tests zeitaufwendig sind und teilweise unsystematisch ablaufen. Der erkannte Änderungsbedarf wird zwar, ebenfalls manuell, dokumentiert und entsprechend ausgeführt, ein erneuter Testdurchlauf stellt jedoch in der Regel keine Rückwirkungsfreiheit auf andere Teile des Systems sicher. Dieser Artikel stellt das Konzept Smart FAT vor, das Konzepte der Hardwareemulation sowie der Prozesssimulation verknüpft und um eine Test-Engine erweitert. Smart FAT ermöglicht es so, die das Leitsystem betreffenden Testreihen an der virtuellen Instanz automatisiert auszuführen.