RT Journal Article
T1 Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma
A1 Fulciniti, Mariateresa
A1 Martínez López, Joaquín
A1 Senapedis, William
A1 Oliva, Stefania
A1 Bandi, Rajya Lakshmi
A1 Amodio, Nicola
A1 Xu, Yan
A1 Szalat, Raphael
A1 Gulla, Annamaria
A1 Samur, Mehmet K.
A1 Roccaro, Aldo
A1 Linares Gómez, María
A1 Cea, Michele
A1 Baloglu, Erkan
A1 Argueta, Christian
A1 Landesman, Yosef
A1 Shacham, Sharon
A1 Liu, Siyuan
A1 Schenone, Monica
A1 Wu, Shiaw-Lin
A1 Karger, Barry
A1 Prabhala, Rao
A1 Anderson, Kenneth C.
A1 Munshi, Nikhil C.
AB 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.
PB American Society of Hematology
SN 0006-4971
YR 2017
FD 2017
LK https://hdl.handle.net/20.500.14352/93559
UL https://hdl.handle.net/20.500.14352/93559
LA eng
NO Fulciniti M, Martinez-Lopez J, Senapedis W, Oliva S, Lakshmi Bandi R, Amodio N, et al. Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma. Blood 2017;129:2233–45. https://doi.org/10.1182/blood-2016-06-724831.
NO Ron and Anita Wornick Fund
NO National Institutes of Health National Cancer Institute
NO Department of Veterans Affairs Merit Review
NO Centro Nacional de Investigaciones Oncológicas (España)
DS Docta Complutense
RD 22 abr 2025