Please use this identifier to cite or link to this item:
Title: Synthetically lethal nanoparticles for treatment of endometrial cancer
Authors: Kareem Ebeid
Xiangbing Meng
Kristina W. Thiel
Anh Vu Do
Sean M. Geary
Angie S. Morris
Erica L. Pham
Amaraporn Wongrakpanich
Yashpal S. Chhonker
Daryl J. Murry
Kimberly K. Leslie
Aliasger K. Salem
University of Iowa
University of Nebraska Medical Center
Mahidol University
University of Iowa Healthcare
Keywords: Chemical Engineering;Engineering;Materials Science;Physics and Astronomy
Issue Date: 1-Jan-2018
Citation: Nature Nanotechnology. Vol.13, No.1 (2018), 72-81
Abstract: © 2017 The Author(s). Uterine serous carcinoma, one of the most aggressive types of endometrial cancer, is characterized by poor outcomes and mutations in the tumour suppressor p53. Our objective was to engender synthetic lethality to paclitaxel (PTX), the frontline treatment for endometrial cancer, in tumours with mutant p53 and enhance the therapeutic efficacy using polymeric nanoparticles (NPs). First, we identified the optimal NP formulation through comprehensive analyses of release profiles and cellular-uptake and cell viability studies. Not only were PTX-loaded NPs superior to PTX in solution, but the combination of PTX-loaded NPs with the antiangiogenic molecular inhibitor BIBF 1120 (BIBF) promoted synthetic lethality specifically in cells with the loss-of-function (LOF) p53 mutation. In a xenograft model of endometrial cancer, this combinatorial therapy resulted in a marked inhibition of tumour progression and extended survival. Together, our data provide compelling evidence for future studies of BIBF- and PTX-loaded NPs as a therapeutic opportunity for LOF p53 cancers.
ISSN: 17483395
Appears in Collections:Scopus 2018

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.