Harnessing Tumor Evolution to Circumvent Resistance

Trends Genet. 2018 Aug;34(8):639-651. doi: 10.1016/j.tig.2018.05.007. Epub 2018 Jun 11.


High-throughput sequencing can be used to measure changes in tumor composition across space and time. Specifically, comparisons of pre- and post-treatment samples can reveal the underlying clonal dynamics and resistance mechanisms. Here, we discuss evidence for distinct modes of tumor evolution and their implications for therapeutic strategies. In addition, we consider the utility of spatial tissue sampling schemes, single-cell analysis, and circulating tumor DNA to track tumor evolution and the emergence of resistance, as well as approaches that seek to forestall resistance by targeting tumor evolution. Ultimately, characterization of the (epi)genomic, transcriptomic, and phenotypic changes that occur during tumor progression coupled with computational and mathematical modeling of tumor evolutionary dynamics may inform personalized treatment strategies.

Keywords: clonal dynamics; computational modeling; therapeutic resistance; tissue correlative studies; tumor evolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism*
  • Clonal Evolution / genetics
  • Computer Simulation
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics
  • Genetic Heterogeneity
  • Humans
  • Models, Biological*
  • Molecular Targeted Therapy
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Radiation Tolerance / genetics


  • Biomarkers, Tumor