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Updated: Jun 12, 2025

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
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Dual-modified antisense oligonucleotides targeting oncogenic protocadherin to treat gastric cancer

Mitsuro Kanda1, Yuuya Kasahara2, Dai Shimizu3

  • 1Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. m-kanda@med.nagoya-u.ac.jp.

British Journal of Cancer
|September 20, 2024
PubMed
Abstract

Insights

Novel antisense oligonucleotides targeting protocadherin alpha 11 (PCDHA11) effectively inhibit gastric cancer cell proliferation and metastasis. This PCDHA11-targeting strategy shows promise for treating gastric cancer and other solid tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Development

Background:

  • Gastric cancer presents a significant global health challenge.
  • Protocadherin alpha 11 (PCDHA11) has been implicated in cancer cell proliferation.
  • Targeting specific genes offers a potential therapeutic avenue.

Purpose of the Study:

  • To develop and evaluate antisense oligonucleotides (ASOs) targeting PCDHA11 for gastric cancer treatment.
  • To investigate the role of PCDHA11 in gastric cancer progression.
  • To assess the efficacy and safety of novel amido-bridged nucleic acid (AmNA)-modified ASOs.

Main Methods:

  • Designed and screened 54 AmNA-modified ASOs for PCDHA11 knockdown.
  • Assessed ASO impact on gastric cancer cell functions and signaling pathways (AKT/mTOR, Wnt/β-catenin, JAK/STAT).
  • Evaluated ASO efficacy in mouse models of gastric cancer metastasis and tumor growth.

Main Results:

  • AmNA-modified anti-PCDHA11 ASOs significantly reduced gastric cancer cell proliferation and metastasis.
  • PCDHA11 overexpression was linked to enhanced cell proliferation.
  • ASO treatment inhibited tumor growth in vivo but caused reversible liver damage.

Conclusions:

  • AmNA-modified anti-PCDHA11 ASOs represent a promising therapeutic strategy for gastric cancer.
  • This approach may also be effective against other solid malignancies.
  • Further research is warranted to optimize ASO therapy and mitigate side effects.

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