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YAP/TAZ-Inhibitor-Based Drug Delivery System for Cancer Therapy

Zhang, Ziqian (2020) YAP/TAZ-Inhibitor-Based Drug Delivery System for Cancer Therapy. Master's Thesis, University of Pittsburgh. (Unpublished)

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The YES-associated protein (YAP) and the transcriptional co-activator with PDZ-binding motif (TAZ) are two important transcriptional co-activators in the Hippo signaling pathway, which play an essential role in organ size control, tumor suppression, tissue regeneration and stem cell self-renewal. However, aberrant activation of YAP and TAZ due to deregulation of the Hippo pathway or overexpression of YAP/TAZ and TEADs can promote cancer development. Hence, pharmacological inhibition of YAP and TAZ may be a useful approach to treat tumors with high YAP/TAZ activity. Here, we developed a YAP/TAZ-inhibitor (niflumic acid (NA))-based drug delivery system for enhanced cancer therapy. Through disrupting the interaction between the TEA domain transcription factors (TEADs) and YAP/TAZ, NA reduces the expression of downstream genes that promote tumor proliferation and migration. At the same time, other hydrophobic anti-cancer drug can be co-delivered to tumor site to improve the overall antitumor activity and decrease side effect. Our strategy may not only improve delivery of well-established anti-cancer drugs, but also further improve their efficacy through inhibiting YAP/TAZ activity.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Zhang, Ziqianziz49@pitt.eduziz490000-0001-9294-660X
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLi, Songsol4@pitt.edusol4
Committee MemberWang,
Committee MemberSant, Vinayakvis45@pitt.eduvis45
Committee MemberYang, Dadyang@pitt.edudyang
Thesis AdvisorLi, Songsol4@pitt.edusol4
Date: 9 April 2020
Date Type: Publication
Defense Date: 3 April 2020
Approval Date: 9 April 2020
Submission Date: 7 April 2020
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 41
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: YAP ;TAZ; TEAD; Niflumic Acid; Dasatinib
Date Deposited: 09 Apr 2020 11:30
Last Modified: 09 Apr 2020 11:30


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