Dissertation/Thesis Abstract

Hemmung des PI3K-Signalweges im Ovarialkarzinom
by Kurz, Antje, Ph.D., Bayerische Julius-Maximilians-Universitaet Wuerzburg (Germany), 2014, 124; 10721844
Abstract (Summary)

Purpose

Platinum resistance is the most crucial problem for treatment of ovarian cancer. There is a clinical need for new treatment strategies which overcome platinum resistance. Recently high level of AKT was shown to be involved in platinum resistance and furthermore in resistance against Natural-killer (NK)-cell mediated killing in ovarian cancer.

Methods

Here, we investigate the ability of the PI3K/AKT inhibitor AEZS-126 alone and in combination with rapamycin to selectively target ovarian cancer cell proliferation and survival in vitro by MTT-assays and FACS based analysis. Furthermore the mechanism of cytotoxicity is analysed by FACS based assays. The NK-killing efficiency of ovarian cancer cells with and without pre-treatment with AEZS-126 was analysed.

Results

AEZS-126 showed good anti-tumour activity in in vitro models of ovarian cancer. Main mechanism of cytotoxicity seems to be necroptosis which could be abrogated by co-incubation with necrostatin-1. Furthermore pre-treatment of platinum resistant cells with AEZS-126 resulted in an increased accessibility of these tumour cells for killing by NK-cells.

Conclusion

We demonstrated the highly efficient anti-tumour activity of AEZS-126 in in vitro models of ovarian cancer. Due to the good anti-tumour activity and the expected increase in NK-cell mediated killing even of platinum resistant tumour cells, AEZS-126 seems to be a promising candidate for clinical testing in ovarian cancer.

Indexing (document details)
Advisor: Hönig , Arnd , Eilers , Martin
Commitee:
School: Bayerische Julius-Maximilians-Universitaet Wuerzburg (Germany)
School Location: Germany
Source: DAI-C 81/1(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Oncology
Keywords: Ovarian cancer
Publication Number: 10721844
ISBN: 9781392406373
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