Inducing stable reversion to achieve cancer control

Journal name:
Nature Reviews Cancer
Volume:
16,
Pages:
266–270
Year published:
DOI:
doi:10.1038/nrc.2016.12
Published online

Abstract

How can we stop cancer progression? Current strategies depend on modelling progression as the balanced outcome of mutations in, and expression of, tumour suppressor genes and oncogenes. New treatments emerge from successful attempts to tip that balance, but secondary mutational escape from those treatments has become a major impediment because it leads to resistance. In this Opinion article, we argue for a return to an earlier stratagem: tumour cell reversion. Treatments based on selection and analysis of stable revertants could create more durable remissions by reducing the selective pressure that leads to rapid drug resistance.

At a glance

Figures

  1. Mechanisms of stable reversion.
    Figure 1: Mechanisms of stable reversion.

    Revertants isolated from viral oncogene-transformed cells can either be phenotypically normal (green cells) or have only partially regained normalcy (blue cells). For example, certain revertants that regain normal growth factor dependency can still form colonies in suspension46. Completely normal revertants can arise either through loss of the viral oncogene or by other genetic changes that in some cases include dramatic alterations of chromosomal composition7. Blue indicates cells with either a malignant or partially malignant state, and green indicates a normal cell or a cancer cell that has fully reverted its phenotype back to normal growth control.

  2. Proposed studies of genetic reversion of cancer cells.
    Figure 2: Proposed studies of genetic reversion of cancer cells.

    The steps in our proposed studies are outlined. CRISPR–Cas9, clustered regularly interspaced short palindromic repeats–CRISPR-associated protein 9; FUdR, 5-fluoro-2'-deoxyuridine; sgRNA, single guide RNA.

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Affiliations

  1. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA; and at Stony Brook University, Stony Brook, New York 11794, USA.

    • Scott Powers
  2. Columbia University, New York 10027, USA.

    • Robert E. Pollack

Competing interests statement

The authors declare no competing interests.

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Author details

  • Scott Powers

    Scott Powers received his Ph.D. in Biological Sciences from Columbia University, New York, USA, in 1983, where he began his career in cancer genetics as a student in the laboratory of Robert E. Pollack. He is currently Director of Cancer Genomics and Professor of Pathology at Stony Brook University, New York, and Research Professor at Cold Spring Harbor Laboratory, New York.

  • Robert E. Pollack

    Robert E. Pollack received his Ph.D. in microbiology from Brandeis University, Waltham, Massachusetts, USA, in 1966. He isolated the first non-tumorigenic revertant cell lines as a postdoctoral Fellow in Pathology at New York University, USA, in 1968. He subsequently did research at Cold Spring Harbor Laboratory, New York, and has been Professor of Biology at Columbia University, New York, since 1978.

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