ArticleMolecular cancer therapeutics2021
PAK4-NAMPT Dual Inhibition Sensitizes Pancreatic Neuroendocrine Tumors to Everolimus.
Article in Molecular cancer therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Computational Identification of New Dual PAK4 and NAMPT Inhibitors.International journal of molecular sciences · 2026Article
- Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.Oncology research · 2026Review
- P21-activated kinase 4: a potent oncogene, molecular mechanisms and opportunities for targeted therapy.Cancer cell international · 2025Review
- Article
- Molecular Characterization and Clinical Outcomes of Pancreatic Neuroendocrine Neoplasms Harboring PAK4-NAMPT Alterations.JCO oncology advances · 2025Article
- Comprehensive multi-omics analysis identifies NUSAP1 as a potential prognostic and immunotherapeutic marker for lung adenocarcinoma.International journal of medical sciences · 2025Article
- Computational drug discovery pipelines identify NAMPT as a therapeutic target in neuroendocrine prostate cancer.Clinical and translational science · 2024Article
- Targeting guanine nucleotide exchange factors for novel cancer drug discovery.Expert opinion on drug discovery · 2024Review
- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- Novel RICTOR amplification harbouring entities: FISH validation of RICTOR amplification in tumour tissue after next-generation sequencing.Scientific reports · 2023Article
- Novel Therapeutic Strategies Exploiting the Unique Properties of Neuroendocrine Neoplasms.Cancers · 2023Article
- PAK4 inhibition significantly potentiates Gemcitabine activity in PDAC cells via inhibition of Wnt/β-catenin, p-ERK/MAPK and p-AKT/PI3K pathways.Biochemistry and biophysics reports · 2023Article
- Review of various NAMPT inhibitors for the treatment of cancer.Frontiers in pharmacology · 2022Review
- Recent advances on development of p21-activated kinase 4 inhibitors as anti-tumor agents.Frontiers in pharmacology · 2022Review
- Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
Metastatic pancreatic neuroendocrine tumors (PNET) remain an unmet clinical problem. Chronologic treatment in PNETs includes observation (watchful protocol), surgery, targeted therapy, and chemotherapy. However, increasing evidence illustrates that the outcomes of targeted therapeutic options for the treatment of advanced PNETs show minimal response. The FDA-approved mTOR inhibitor everolimus does not shrink these tumors. It only delays disease progression in a subset of patients, while a significant fraction acquires resistance and shows disease progression. Thus, there is a need for more effective targeted approaches to sensitize PNETs to everolimus for better treatment outcomes. Previously, we showed that mTOR regulator p21 activated kinase 4 (PAK4) and nicotinamide adenine dinucleotide biosynthesis enzyme nicotinamide phosphoribosyl transferase (NAMPT) were aberrantly expressed in PNET tissue and promoted everolimus resistance. In this report, we demonstrate that PAK4-NAMPT dual inhibitor KPT-9274 can synergize with everolimus (growth inhibition, colony suppression, and glucose uptake assays). KPT-9274-everolimus disrupted spheroid formation in multiple PNET models. Molecular analysis showed alteration of mTORC2 through downregulation of RICTOR as a mechanism supporting synergy with everolimus
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.