The effect of cellular differentiation on the development of permanent drug resistance

Andrew J. Coldman, James H. Goldie, Vincent To Yee Ng

Research output: Journal article publicationJournal articleAcademic researchpeer-review

23 Citations (Scopus)

Abstract

A stem cell compartment model is utilized to simulate the growth of human tumors. This model is used to explore the effect of cell differentiation and loss on the development of spontaneous drug resistance. Cellular differentiation is found to increase the rate of development of single drug resistance, although this is balanced by the likehood that such resistant cells will subsequently become extinct. Overall the probability that singly resistant cells will develop and persist is found to be independent of the rate of cellular differentiation. Conversely, when two drugs are available, the probability that cells resistant to both drugs will persist is proportional to the rate of cellular differentiation. Approximate formulae relating the net overall mutation rate to the intrinsic mutation rates and net growth rates of the stem cell compartment are developed.
Original languageEnglish
Pages (from-to)177-198
Number of pages22
JournalMathematical Biosciences
Volume74
Issue number2
DOIs
Publication statusPublished - 1 Jan 1985
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Ecology, Evolution, Behavior and Systematics

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