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The impact of non-genetic heterogeneity on cancer cell death

Zintis Inde1, Scott J Dixon1,2

  • 1a Cancer Biology Program , Stanford University School of Medicine , Stanford , CA , USA.

Critical Reviews in Biochemistry and Molecular Biology
|December 19, 2017
PubMed

Insights

Cancer cells exhibit non-genetic variation, leading to drug tolerance. This cellular heterogeneity can cause chemotherapy failure and promote the development of drug resistance.

Area of Science:

  • Oncology
  • Cell Biology
  • Genetics

Background:

  • Cancer chemotherapy aims for uniform cancer cell death.
  • Individual cancer cells display molecular differences, affecting drug sensitivity.
  • Genetic alterations can drive drug resistance, but non-genetic factors are increasingly recognized.

Purpose of the Study:

  • To explore the role of non-genetic variation in cancer drug tolerance.
  • To understand how non-genetic heterogeneity contributes to chemotherapy failure.

Main Methods:

  • Analysis of molecular variations within cancer cell populations.
  • Investigation of epigenetic, gene expression, and metabolic factors.
  • Assessment of drug sensitivity and cell death pathways.

Main Results:

  • Non-genetic variations create drug-tolerant states in cancer cells.
  • These states persist for hours to weeks, reducing drug sensitivity.
  • Non-genetic heterogeneity provides a foundation for genetic resistance.

Conclusions:

  • Non-genetic variation is a critical factor in cancer drug tolerance and treatment failure.
  • Understanding non-genetic heterogeneity is essential for developing more effective cancer therapies.
  • Targeting non-genetic states may overcome or prevent drug resistance.
Keywords:
Cell deathapoptosiscancerheterogeneitysingle-cell

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