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Mechanisms of targeted therapy resistance take a de-TOR

Leanna R Gentry1, Timothy D Martin, Channing J Der

  • 1Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Cancer Cell
|September 14, 2013
PubMed

Insights

Cancer drug resistance can arise from multiple pathways. Two studies reveal that mTOR activation is a common mechanism causing resistance to Raf-MEK-ERK and PI3K signaling inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • Cancer therapeutics often target critical signal transduction pathways.
  • Therapeutic effectiveness is frequently limited by drug resistance.
  • Mechanisms of resistance are diverse, including de novo and acquired resistance.

Purpose of the Study:

  • To investigate common mechanisms underlying resistance to cancer therapeutics.
  • To identify convergence points in resistance pathways.
  • To explore the role of mTOR activation in resistance to Raf-MEK-ERK and PI3K inhibitors.

Main Methods:

  • Analysis of recent studies on cancer drug resistance.
  • Identification of key signaling pathways involved in resistance.
  • Focus on mechanistic insights into mTOR activation.

Main Results:

  • Two studies highlight mTOR activation as a convergence point for resistance mechanisms.
  • mTOR activation contributes to resistance against inhibitors of the Raf-MEK-ERK pathway.
  • mTOR activation also drives resistance to PI3K signaling inhibitors.

Conclusions:

  • mTOR activation represents a central mechanism in acquired resistance to targeted cancer therapies.
  • Understanding mTOR's role is crucial for overcoming resistance to Raf-MEK-ERK and PI3K inhibitors.
  • Targeting mTOR may offer a strategy to re-sensitize tumors to these therapies.

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