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Updated: Aug 28, 2025

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Recent advances on development of p21-activated kinase 4 inhibitors as anti-tumor agents

Yang Li1, Qing Lu1, Chenghu Xie1

  • 1Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.

Frontiers in Pharmacology
|September 15, 2022
PubMed

Insights

P21-activated kinase 4 (PAK4) is overexpressed in tumors and inhibiting it can slow cancer growth and enhance immunotherapy. Recent research focuses on developing PAK4 inhibitors for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • P21-activated kinase 4 (PAK4) is a key signaling protein.
  • PAK4 is frequently overexpressed in various human cancers.
  • PAK4 activity drives cancer cell proliferation, migration, and invasion.

Purpose of the Study:

  • To review recent advancements in understanding PAK4-mediated signaling pathways.
  • To highlight the development of small molecule PAK4 inhibitors over the past five years.
  • To discuss the potential of PAK4 inhibition in cancer therapy, including immunotherapy sensitization.

Main Methods:

  • Literature review of recent research on PAK4 signaling and inhibitors.
  • Analysis of published data on PAK4 inhibitor efficacy and preclinical/clinical studies.
  • Discussion of emerging trends and challenges in PAK4-targeted drug development.

Main Results:

  • Pharmacological inhibition of PAK4 effectively reduces cancer cell proliferation, migration, and invasion.
  • PAK4 inhibition has shown promise in sensitizing tumors to immunotherapy.
  • Several PAK4 inhibitors have been developed, with KPT-9274 entering Phase I clinical trials.

Conclusions:

  • PAK4 is a promising therapeutic target for various cancers.
  • The development of PAK4 inhibitors represents a significant advancement in cancer treatment strategies.
  • Future research should focus on overcoming current challenges and exploring new developmental directions for PAK4 inhibitors.
Keywords:
clinical progressimmune infiltrationoncotherapyp21-activated kinase 4small molecular inhibitors

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