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Transient Autophagy Inhibition Precipitates Oncogenesis: A Red Flag For Pharmacological Autophagy Inhibitors?

Lorenzo Galluzzi1, Guido Kroemer2

  • 1Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA; Sandra and Edward Meyer Cancer Center, New York, NY, USA; Caryl and Israel Englander Institute for Precision Medicine, New York, NY, USA; Department of Dermatology, Yale School of Medicine, New Haven, CT, USA; Université de Paris, Paris, France.

Trends in Cell Biology
|April 18, 2020
PubMed

Insights

Transient genetic inhibition of autophagy promotes aging diseases in mice. Restoring autophagy helps aging but worsens tumors, limiting its cancer therapy potential.

Area of Science:

  • Cellular Biology
  • Oncology
  • Aging Research

Background:

  • Autophagy, a cellular degradation process, plays a dual role in aging and cancer.
  • Previous studies suggested therapeutic potential for modulating autophagy.

Purpose of the Study:

  • To investigate the effects of transient autophagy inhibition on age-associated pathologies.
  • To evaluate the impact of autophagy restoration on tumor development.

Main Methods:

  • Genetic manipulation to inhibit autophagy transiently in mouse models.
  • Monitoring of age-related disease markers.
  • Assessment of tumor incidence and progression following autophagy modulation.

Main Results:

  • Transient genetic inhibition of autophagy accelerated the onset of age-associated pathologies in mice.
  • Restoration of autophagy ameliorated these age-related disorders.
  • However, autophagy restoration significantly increased the incidence of both solid and hematological tumors.

Conclusions:

  • Autophagy inhibition presents a complex therapeutic challenge.
  • While potentially beneficial for aging, its pro-tumorigenic effects warrant caution for cancer treatment strategies.
Keywords:
ATG5cardiac fibrosischemosensitizationimmunosurveillancelongevityneurodegeneration

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