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Role of FoxO Proteins in Cellular Response to Antitumor Agents

Giovanni Luca Beretta1, Cristina Corno2, Nadia Zaffaroni3

  • 1Molecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy. giovanni.beretta@istitutotumori.mi.it.

Cancers
|January 17, 2019
PubMed

Insights

Forkhead box proteins (FoxOs) influence cancer cell responses to antitumor drugs. Modulating FoxO levels and localization can enhance sensitivity to treatments like cisplatin and gefitinib, impacting drug resistance.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Pharmacology

Background:

  • Forkhead box proteins (FoxOs) are transcription factors regulating cell cycle, apoptosis, and drug resistance.
  • FoxOs' activity is modulated by post-translational modifications and microRNA networks.
  • Altered FoxO expression is linked to tumor cell resistance to various anticancer agents.

Purpose of the Study:

  • To review the role of FoxO transcription factors in tumor cell response to drug treatment.
  • To discuss the impact of FoxO expression on drug sensitivity and resistance.
  • To explore therapeutic strategies targeting FoxO localization for improved cancer treatment.

Main Methods:

  • Literature review of studies investigating FoxO proteins in cancer drug response.
  • Analysis of the impact of post-translational modifications and microRNAs on FoxO activity.
  • Examination of specific FoxO family members (FoxO1, FoxO3) in relation to drug sensitivity.

Main Results:

  • Reduced FoxO1 expression correlates with resistance to cisplatin and reduced efficacy of drug combinations in ovarian cancer.
  • FoxO3 mediates cisplatin toxicity in colorectal cancer and is required for gefitinib-induced apoptosis.
  • Nuclear retention of FoxO1 enhances sensitivity to cisplatin by promoting pro-apoptotic gene expression.

Conclusions:

  • FoxO proteins play a critical role in modulating tumor cell sensitivity and resistance to anticancer drugs.
  • Targeting FoxO1 localization presents a promising strategy to overcome drug resistance.
  • Understanding FoxO function is crucial for developing novel therapeutic approaches in oncology.
Keywords:
FoxOdrug resistancetumor

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