Tumor heterogeneity and progression: Conceptual foundations for modeling

Larry D. Greller, Frank L. Tobin, George Poste

Research output: Contribution to journalReview article

64 Scopus citations

Abstract

A conceptual foundation for modeling tumor progression, growth, and heterogeneity is presented. The purpose of such models is to aid understanding, test ideas, formulate experiments, and to model cancer 'in machina' to address the dynamic features of tumor cell heterogeneity, progression, and growth. The descriptive capabilities of such an approach provides a consistent language for qualitatively reasoning about tumor behavior. This approach provides a schema for building conceptual models that combine three key phenomenological driving elements: growth, progression, and genetic instability. The growth element encompasses processes contributing to changes in tumor bulk and is distinct from progression per se. The progression element subsumes a broad collection of processes underlying phenotypic progression. The genetics element represents heritable changes which potentially affect tumor character and behavior. Models, conceptual and mathematical, can be built for different tumor situations by drawing upon the interaction of these three distinct driving elements. These models can be used as tools to explore a diversity of hypotheses concerning dynamic changes in cellular populations during tumor progression, including the generation of intratumor heterogeneity. Such models can also serve to guide experimentation and to gain insight into dynamic aspects of complex tumor behavior.

Original languageEnglish (US)
Pages (from-to)177-208
Number of pages32
JournalInvasion and Metastasis
Volume16
Issue number4-5
StatePublished - Dec 1 1996
Externally publishedYes

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Keywords

  • Genetic instability
  • Growth
  • Mathematical modeling
  • Tumor heterogeneity
  • Tumor progression
  • Tumorigenesis

ASJC Scopus subject areas

  • Cancer Research

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