%0 Journal Article
%A Fulciniti, Mariateresa 
%A Martínez López, Joaquín
%A Senapedis, William 
%A Oliva, Stefania 
%A Bandi, Rajya Lakshmi 
%A Amodio, Nicola 
%A Xu, Yan 
%A Szalat, Raphael 
%A Gulla, Annamaria 
%A  Samur, Mehmet K.
%A Roccaro, Aldo 
%A Linares Gómez, María
%A Cea, Michele 
%A Baloglu, Erkan 
%A Argueta, Christian 
%A Landesman, Yosef 
%A Shacham, Sharon 
%A Liu, Siyuan 
%A Schenone, Monica 
%A Wu, Shiaw-Lin 
%A Karger, Barry 
%A Prabhala, Rao 
%A Anderson, Kenneth C. 
%A Munshi, Nikhil C. 
%T Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma
%D 2017
%@ 0006-4971
%U https://hdl.handle.net/20.500.14352/93559
%X Dysregulated oncogenic serine/threonine kinases play a pathological role in diverse forms of malignancies, including multiple myeloma (MM), and thus represent potential therapeutic targets. Here, we evaluated the biological and functional role of p21-activated kinase 4 (PAK4) and its potential as a new target in MM for clinical applications. PAK4 promoted MM cell growth and survival via activation of MM survival signaling pathways, including the MEK-extracellular signal-regulated kinase pathway. Furthermore, treatment with orally bioavailable PAK4 allosteric modulator (KPT-9274) significantly impacted MM cell growth and survival in a large panel of MM cell lines and primary MM cells alone and in the presence of bone marrow microenvironment. Intriguingly, we have identified FGFR3 as a novel binding partner of PAK4 and observed significant activity of KPT-9274 against t(4;14)-positive MM cells. This set of data supports PAK4 as an oncogene in myeloma and provide the rationale for the clinical evaluation of PAK4 modulator in myeloma.
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