Cancer systems biology in the genome sequencing era: part 2, evolutionary dynamics of tumor clonal networks and drug resistance

Semin Cancer Biol. 2013 Aug;23(4):286-92. doi: 10.1016/j.semcancer.2013.06.001. Epub 2013 Jun 18.


A tumor often consists of multiple cell subpopulations (clones). Current chemo-treatments often target one clone of a tumor. Although the drug kills that clone, other clones overtake it and the tumor recurs. Genome sequencing and computational analysis allows to computational dissection of clones from tumors, while singe-cell genome sequencing including RNA-Seq allows profiling of these clones. This opens a new window for treating a tumor as a system in which clones are evolving. Future cancer systems biology studies should consider a tumor as an evolving system with multiple clones. Therefore, topics discussed in Part 2 of this review include evolutionary dynamics of clonal networks, early-warning signals (e.g., genome duplication events) for formation of fast-growing clones, dissecting tumor heterogeneity, and modeling of clone-clone-stroma interactions for drug resistance. The ultimate goal of the future systems biology analysis is to obtain a 'whole-system' understanding of a tumor and therefore provides a more efficient and personalized management strategies for cancer patients.

Keywords: Cancer evolution; Drug resistance; Early-warning signal; Genome sequencing; Personalized medicine; Signaling network; Systems biology; Tumor clone; Tumor heterogeneity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Lineage / genetics
  • Gene Regulatory Networks
  • Genome, Human / genetics*
  • Humans
  • Models, Genetic
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Sequence Analysis, DNA / methods*
  • Single-Cell Analysis / methods
  • Systems Biology / methods*
  • Tumor Microenvironment / genetics