Publication: Synthetically lethal nanoparticles for treatment of endometrial cancer
Issued Date
2018-01-01
Resource Type
ISSN
17483395
17483387
17483387
Other identifier(s)
2-s2.0-85036544040
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Nanotechnology. Vol.13, No.1 (2018), 72-81
Suggested Citation
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 Synthetically lethal nanoparticles for treatment of endometrial cancer. Nature Nanotechnology. Vol.13, No.1 (2018), 72-81. doi:10.1038/s41565-017-0009-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/45457
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Synthetically lethal nanoparticles for treatment of endometrial cancer
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.