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Title: A novel PAK4 inhibitor suppresses pancreatic cancer growth and enhances the inhibitory effect of gemcitabine.
Austin Authors: He, Hong ;Dumesny, Chelsea;Ang, Ching-Seng;Dong, Li;Ma, Yi;Zeng, Jun;Nikfarjam, Mehrdad 
Affiliation: Surgery (University of Melbourne)
Pakinax Pty. Ltd., Melbourne, Australia
Bio21 Institute, University of Melbourne, Flemington Road, Parkville, Victoria, Australia
Issue Date: Feb-2022
Date: 2021-12-29
Publication information: Translational Oncology 2021; 16: 101329
Abstract: Over 95% of Pancreatic ductal adenocarcinomas (PDA) carry mutations in the oncogene KRas which has been proven to be a difficult drug target. P21-activated kinase 4 (PAK4), acts downstream of KRas, and is overexpressed in PDA contributing to its growth and chemoresistance, and thus becomes an attractive therapeutic target. We have developed a new PAK4 inhibitor, PAKib and tested its effect on pancreatic cancer (PC) cell growth in vitro and in a syngeneic mouse model of PC. PAKib suppressed PC cell growth by inducing cell death and cycle arrest. PAKib inhibited PC growth and enhanced the inhibition by gemcitabine of PC in cell culture and in PC mouse model. PAKib acted through multiple signaling pathways involved in cell cycle checkpoints, apoptosis, cell junction, and focal adhesion. These proof-of-concept studies demonstrated the anti-cancer effect of PAKib alone and in combination with gemcitabine and warrant a further clinical investigation.
DOI: 10.1016/j.tranon.2021.101329
ORCID: 0000-0003-4866-276X
Journal: Translational Oncology
PubMed URL: 34973571
PubMed URL:
ISSN: 1936-5233
Type: Journal Article
Subjects: Gemcitabine
Pancreatic cancer
Appears in Collections:Journal articles

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