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Study of Protein-protein Interactions in Autophagy Research
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Autophagy induction by IGF1R inhibition with picropodophyllin and linsitinib

Qi Wu1,2,3, Ai-Ling Tian2,3,4, Guido Kroemer2,3,5,6,7

  • 1Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

Autophagy
|June 10, 2021
PubMed

Insights

Insulin-like growth factor 1 receptor (IGF1R) inhibition with picropodophyllin (PPP) enhances cancer cell death and immune response. This strategy improves chemoimmunotherapy efficacy, offering a novel approach for cancer treatment.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Autophagy induction is a strategy to enhance antineoplastic therapies.
  • Autophagy facilitates immunogenic cancer cell death and immune recognition.
  • Current strategies aim to improve cancer treatment outcomes via immune modulation.

Purpose of the Study:

  • To identify novel autophagy inducers for cancer therapy.
  • To investigate the role of IGF1R inhibition in autophagy and cancer treatment.
  • To evaluate the therapeutic potential of IGF1R inhibitors in chemoimmunotherapy.

Main Methods:

  • Phenotypic screening of 65,000 compounds for autophagy induction.
  • In vitro and in vivo experiments using IGF1R inhibitors (picropodophyllin and linsitinib).
  • Analysis of adenosine triphosphate (ATP) release from cancer cells.
  • Correlation analysis of IGF1R phosphorylation with autophagy, immune profile, and prognosis in triple-negative breast cancer.

Main Results:

  • Picropodophyllin (PPP) was identified as a potent inducer of autophagic flux.
  • PPP inhibits IGF1R tyrosine kinase activity, enhancing ATP release from stressed cancer cells.
  • IGF1R inhibition improved chemoimmunotherapy efficacy in preclinical cancer models.
  • Linsitinib, another IGF1R inhibitor, phenocopied PPP's effects.
  • In human triple-negative breast cancer, high IGF1R phosphorylation correlated with reduced autophagy and poor prognosis.

Conclusions:

  • IGF1R inhibition is a potent strategy to induce autophagy and enhance immunogenic cancer cell death.
  • IGF1R inhibitors can improve the efficacy of chemoimmunotherapy.
  • IGF1R inhibition represents a promising novel therapeutic strategy for cancer treatment.
Keywords:
Anticancer immunitybiosensordrug discoveryhigh-content screeningimmunogenic cell death

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