Journal article
Synthetically lethal nanoparticles for treatment of endometrial cancer
Nature nanotechnology, Vol.13(1), pp.72-81
01/2018
DOI: 10.1038/s41565-017-0009-7
PMCID: PMC5762267
PMID: 29203914
Abstract
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.
Details
- Title: Subtitle
- Synthetically lethal nanoparticles for treatment of endometrial cancer
- Creators
- Kareem Ebeid - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USAXiangbing Meng - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USAKristina W Thiel - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USAAnh-Vu Do - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USASean M Geary - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USAAngie S Morris - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USAErica L Pham - Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, USAAmaraporn Wongrakpanich - Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, ThailandYashpal S Chhonker - Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USADaryl J Murry - Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USAKimberly K Leslie - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. kimberly-leslie@uiowa.eduAliasger K Salem - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA. aliasger-salem@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Nature nanotechnology, Vol.13(1), pp.72-81
- DOI
- 10.1038/s41565-017-0009-7
- PMID
- 29203914
- PMCID
- PMC5762267
- NLM abbreviation
- Nat Nanotechnol
- ISSN
- 1748-3395
- eISSN
- 1748-3395
- Publisher
- England
- Grant note
- P30 ES005605 / NIEHS NIH HHS T90 DE023520 / NIDCR NIH HHS R01 CA184101 / NCI NIH HHS R01 CA099908 / NCI NIH HHS P30 CA086862 / NCI NIH HHS P50 CA097274 / NCI NIH HHS
- Language
- English
- Date published
- 01/2018
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Obstetrics and Gynecology; Dental Research; Chemical and Biochemical Engineering; Holden Comprehensive Cancer Center
- Record Identifier
- 9983931815102771
Metrics
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