ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Dual PAK4-NAMPT Inhibition Impacts Growth and Survival, and Increases Sensitivity to DNA-Damaging Agents in Waldenström Macroglobulinemia.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Computational Identification of New Dual PAK4 and NAMPT Inhibitors.International journal of molecular sciences · 2026Article
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Peripheral blood mononuclear cell gene expression signatures predict long-term survivorship in canine DLBCL.Scientific reports · 2026Article
- Inhibition of NAMPT targets DNA damage response to sensitize alkylating chemotherapy in TP53 mutant mantle cell lymphoma.Blood advances · 2026Article
- First-in-Human Phase I Study of KPT-9274, a First-in-Class Dual Inhibitor of PAK4 and NAMPT, in Patients with Advanced Solid Malignancies.Targeted oncology · 2026Article
- PAK4 phosphorylates and stabilizes MYC to promote acute myeloid leukemia.Cell insight · 2025Article
- NAD+ metabolism restriction boosts high-dose melphalan efficacy in patients with multiple myeloma.Blood advances · 2025Article
- Unlocking the therapeutic potential of selective CDK7 and BRD4 inhibition against multiple myeloma cell growth.Haematologica · 2025Article
- Channeling Nicotinamide Phosphoribosyltransferase (NAMPT) to Address Life and Death.Journal of medicinal chemistry · 2024Review
- P-21 Activated Kinases in Liver Disorders.Cancers · 2023Review
- Baseline tumor gene expression signatures correlate with chemoimmunotherapy treatment responsiveness in canine B cell lymphoma.PloS one · 2023Article
- Remodeling of the tumor microenvironment through PAK4 inhibition sensitizes tumors to immune checkpoint blockade.Cancer research communications · 2022Article
- Targeting of p21-Activated Kinase 4 Radiosensitizes Glioblastoma Cells via Impaired DNA Repair.Cells · 2022Article
- CORO1C, a novel PAK4 binding protein, recruits phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells.Acta biochimica et biophysica Sinica · 2022Article
- Recent advances on development of p21-activated kinase 4 inhibitors as anti-tumor agents.Frontiers in pharmacology · 2022Review
- PAK4 and NAMPT as Novel Therapeutic Targets in Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Mantle Cell Lymphoma.Cancers · 2021Article
- Advances in NAD-Lowering Agents for Cancer Treatment.Nutrients · 2021Review
- enAsCas12a Enables CRISPR-Directed Evolution to Screen for Functional Drug Resistance Mutations in Sequences Inaccessible to SpCas9.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- NADSignal transduction and targeted therapy · 2021Review
- The Role of p21-Activated Kinases in Cancer and Beyond: Where Are We Heading?Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 4 countries.
Funding
Abstract
purposep21-activated kinase 4 (PAK4) plays a significant biological and functional role in a number of malignancies, including multiple myeloma (MM). On the basis of our promising findings in MM, we here characterize PAK4 expression and role in WM cells, as well effect of dual PAK4-NAMPT inhibitor (KPT-9274) against WM cell growth and viability. EXPERIMENTAL
designWe have analyzed mRNA and protein expression levels of PAK4 in WM cells, and used loss-of-function approach to investigate its contribution to WM cell viability. We have further tested the
resultsWe report here high-level expression and functional role of PAK4 in WM, as demonstrated by shRNA-mediated knockdown; and significant impact of KPT-9274 on WM cell growth and viability. The growth inhibitory effect of KPT-9274 was associated with decreased PAK4 expression and NAMPT activity, as well as induction of apoptosis. Interestingly, in WM cell lines treated with KPT-9274, we detected a significant impact on DNA damage and repair genes. Moreover, we observed that apart from inducing DNA damage, KPT-9274 specifically decreased RAD51 and the double-strand break repair by the homologous recombination pathway. As a result, when combined with a DNA alkylating agents bendamustine and melphalan, KPT-9274 provided a synergistic inhibition of cell viability in WM cell lines and primary patient WM cells
conclusionsThese results support the clinical investigation of KPT-9274 in combination with DNA-damaging agent for treatment of WM.
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