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Updated: Jan 18, 2026

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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Association between novel agents targeting proprotein convertase subtilisin/kexin type 9 and cancer incidence

Hsueh-Ju Lu1,2, Shiow-Ing Wang3,4, Wei-Shiou Huang1,2

  • 1Division of Hematology and Oncology, Department of Internal Medicine, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Rd., South District, Taichung, 40201, Taiwan.

Naunyn-Schmiedeberg'S Archives of Pharmacology
|May 30, 2025
PubMed

Insights

Novel PCSK9 inhibitors, including small interfering RNA (siRNA), may reduce cancer incidence compared to monoclonal antibodies. Inclisiran showed a lower cumulative cancer incidence in this study.

Area of Science:

  • Cardiovascular Medicine
  • Oncology
  • Pharmacology

Background:

  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower LDL cholesterol.
  • PCSK9 inhibitors include small interfering RNA (siRNA) and monoclonal antibodies.
  • The impact of PCSK9 inhibitors on cancer incidence requires further investigation.

Purpose of the Study:

  • To compare the cumulative incidence of cancer in patients treated with siRNA inhibitors versus monoclonal antibodies targeting PCSK9.
  • To evaluate the safety profile of inclisiran in relation to cancer risk compared to alirocumab/evolocumab.

Main Methods:

  • Retrospective cohort study using the TriNetX database.
  • Inclusion of patients using PCSK9-targeting agents, divided into siRNA (inclisiran) and monoclonal antibody (alirocumab/evolocumab) groups.
  • 1:1 propensity score matching to compare cancer incidence between groups.

Main Results:

  • The study included 37,226 individuals; 664 in the siRNA group.
  • After matching, the 520-day cumulative cancer incidence was 1.39% for siRNA and 6.58% for monoclonal antibodies (P=.125; aHR=0.463).
  • Sensitivity analyses consistently showed lower cancer incidence with siRNA inhibitors.

Conclusions:

  • Inclisiran may be associated with a lower cumulative incidence of cancer compared to alirocumab/evolocumab.
  • These findings suggest a potential differential effect of PCSK9 inhibitor classes on cancer risk.
  • Further large-scale studies or clinical trials are necessary to validate these results.
Keywords:
Cancer incidenceNovel agentsPCSK9TriNetx database

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