Preventing clonal evolutionary processes in cancer: Insights from mathematical models

Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):8843-50. doi: 10.1073/pnas.1501730112.


Clonal evolutionary processes can drive pathogenesis in human diseases, with cancer being a prominent example. To prevent or treat cancer, mechanisms that can potentially interfere with clonal evolutionary processes need to be understood better. Mathematical modeling is an important research tool that plays an ever-increasing role in cancer research. This paper discusses how mathematical models can be useful to gain insights into mechanisms that can prevent disease initiation, help analyze treatment responses, and aid in the design of treatment strategies to combat the emergence of drug-resistant cells. The discussion will be done in the context of specific examples. Among defense mechanisms, we explore how replicative limits and cellular senescence induced by telomere shortening can influence the emergence and evolution of tumors. Among treatment approaches, we consider the targeted treatment of chronic lymphocytic leukemia (CLL) with tyrosine kinase inhibitors. We illustrate how basic evolutionary mathematical models have the potential to make patient-specific predictions about disease and treatment outcome, and argue that evolutionary models could become important clinical tools in the field of personalized medicine.

Keywords: cancer; clonal evolution; mathematical models; targeted therapy; telomeres.

MeSH terms

  • Cell Lineage
  • Cellular Senescence
  • Clonal Evolution*
  • Humans
  • Models, Biological*
  • Mutation / genetics
  • Neoplasms / drug therapy
  • Neoplasms / pathology*
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology
  • Stem Cells / cytology
  • Stochastic Processes