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Targeting of CDK1 and PRMT5 as a potential therapeutic combination for non-small cell lung cancer

Zhanqiang Zhai1, Chunwei Xu1,2, Yonghua Min1

  • 1Department of Thoracic Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, The Third Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang Province, China.

Histology and Histopathology
|January 5, 2026
PubMed
Abstract

Insights

Targeting protein arginine methyltransferase 5 (PRMT5) and cyclin-dependent kinase 1 (CDK1) shows synergistic anti-tumor effects. This combination therapy is effective in MTAP-deficient non-small cell lung cancer (NSCLC) by inhibiting cell growth and migration.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Protein arginine methyltransferase 5 (PRMT5) is a potential therapeutic target in non-small cell lung cancer (NSCLC).
  • Combination therapies are being explored to enhance treatment efficacy in NSCLC.
  • Identifying synergistic targets is crucial for effective combination strategies.

Purpose of the Study:

  • To identify potential combination therapeutic targets for NSCLC by analyzing PRMT5-related genes.
  • To investigate the synergistic effects of combining PRMT5 inhibitors (PRMT5i) with cyclin-dependent kinase 1 inhibitors (CDK1i) in NSCLC cell lines.

Main Methods:

  • Bioinformatics analysis using The Cancer Genome Atlas (TCGA) and X2K Appyter databases to identify kinases associated with PRMT5.
  • In vitro studies using lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) cell lines to evaluate synergistic effects of PRMT5i and CDK1i.

Main Results:

  • Cyclin-dependent kinase 1 (CDK1) was identified as a key kinase associated with PRMT5 in NSCLC.
  • Both PRMT5 and CDK1 were significantly upregulated in NSCLC tissues.
  • MTAP-null NSCLC cell lines showed sensitivity to PRMT5i monotherapy and a significant synergistic effect when combined with CDK1i, leading to inhibited cell growth and migration.

Conclusions:

  • Targeting both PRMT5 and CDK1 exhibits synergistic anti-tumor effects in MTAP-deficient NSCLC.
  • The combination of PRMT5i and CDK1i represents a promising therapeutic strategy for a subset of NSCLC patients.

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