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Autophagy inhibition in combination cancer treatment

Kristen M Livesey1, Daolin Tang, Herbert J Zeh

  • 1University of Pittsburgh, G.27A Hillman Cancer Center, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.

Current Opinion in Investigational Drugs (London, England : 2000)
|November 28, 2009
PubMed

Insights

Autophagy, a cell survival process, significantly contributes to cancer treatment resistance. Inhibiting autophagy with compounds like chloroquine or targeting HMGB1 offers a promising strategy for a new generation of cancer therapies.

Area of Science:

  • Oncology
  • Cellular Biology
  • Pharmacology

Background:

  • Cancer treatment resistance is a major clinical challenge, driven by various cellular mechanisms.
  • Autophagy, a cellular self-degradation process, plays a critical role in cell survival under stress conditions.
  • Emerging evidence highlights autophagy's significant contribution to resistance against chemotherapy, radiation, and immunotherapy.

Purpose of the Study:

  • To review the role of autophagy in mediating cancer treatment resistance.
  • To explore current and emerging strategies for inhibiting autophagy to overcome treatment resistance.
  • To discuss novel therapeutic agents targeting autophagy for improved cancer treatment outcomes.

Main Methods:

  • Literature review of studies investigating autophagy in cancer.
  • Analysis of mechanisms by which autophagy confers resistance to various cancer therapies.
  • Examination of compounds and strategies aimed at reversing or inhibiting autophagy.

Main Results:

  • Autophagy promotes cancer cell survival during genotoxic stress, nutrient deprivation, and other cellular insults.
  • Autophagy inhibition, using agents like chloroquine, hydroxychloroquine, and clomipramine, can sensitize cancer cells to conventional treatments.
  • Targeting the high-mobility group box-1 (HMGB1) protein, linked to sustained autophagy, presents another therapeutic avenue.

Conclusions:

  • Autophagy is a key mechanism of resistance in cancer treatment, impacting chemotherapy, radiation, and immunotherapy efficacy.
  • Pharmacological inhibition of autophagy, alongside conventional therapies, holds significant potential for enhancing treatment outcomes.
  • Further research and screening for novel autophagy inhibitors are crucial for developing next-generation cancer therapeutics.

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