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Updated: Aug 25, 2025

Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
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Larotrectinib induces autophagic cell death through AMPK/mTOR signalling in colon cancer

Wencheng Kong1,2, Hangzhang Zhu2, Sixing Zheng2

  • 1Zhejiang Province Key Laboratory of Anti-cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Journal of Cellular and Molecular Medicine
|October 17, 2022
PubMed

Insights

Larotrectinib effectively inhibits colon cancer growth and spread by activating AMPK/mTOR-mediated autophagy. This targeted therapy suppresses proliferation, migration, and epithelial-mesenchymal transition in colon cancer cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Tropomyosin receptor kinase (TRK) fusions drive various cancers.
  • Larotrectinib is a TRK inhibitor, but its mechanisms in colon cancer are unclear.

Purpose of the Study:

  • To investigate the molecular mechanisms of Larotrectinib in colon cancer.
  • To explore Larotrectinib's effects on proliferation, migration, EMT, and autophagy.

Main Methods:

  • Cell proliferation and migration assays.
  • Western blotting for EMT markers (E-cadherin, vimentin, MMP-2/9) and autophagy markers (LC3II/LC3I, p62).
  • AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathway analysis.
  • In vivo tumor xenograft model.

Main Results:

  • Larotrectinib suppressed colon cancer cell proliferation and migration.
  • Larotrectinib inhibited epithelial-mesenchymal transition (EMT) by increasing E-cadherin and decreasing vimentin and MMP-2/9.
  • Larotrectinib activated autophagic flux and the AMPK/mTOR pathway.
  • AMPK silencing diminished Larotrectinib's effects on autophagy and EMT.
  • Tumor growth and weight were reduced in Larotrectinib-treated mice.

Conclusions:

  • Larotrectinib suppresses colon cancer progression through AMPK/mTOR-mediated autophagy.
  • Larotrectinib demonstrates therapeutic potential for TRK fusion-positive colon cancer.
Keywords:
AMPK/mTOR signallingLarotrectinibautophagy fluxcolon cancerepithelial-mesenchymal transition

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