Conceptualizing a tool to optimize therapy based on dynamic heterogeneity.
Phys Biol
; 9(6): 065005, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-23197078
Complex biological systems often display a randomness paralleled in processes studied in fundamental physics. This simple stochasticity emerges owing to the complexity of the system and underlies a fundamental aspect of biology called phenotypic stochasticity. Ongoing stochastic fluctuations in phenotype at the single-unit level can contribute to two emergent population phenotypes. Phenotypic stochasticity not only generates heterogeneity within a cell population, but also allows reversible transitions back and forth between multiple states. This phenotypic interconversion tends to restore a population to a previous composition after that population has been depleted of specific members. We call this tendency homeostatic heterogeneity. These concepts of dynamic heterogeneity can be applied to populations composed of molecules, cells, individuals, etc. Here we discuss the concept that phenotypic stochasticity both underlies the generation of heterogeneity within a cell population and can be used to control population composition, contributing, in particular, to both the ongoing emergence of drug resistance and an opportunity for depleting drug-resistant cells. Using notions of both 'large' and 'small' numbers of biomolecular components, we rationalize our use of Markov processes to model the generation and eradication of drug-resistant cells. Using these insights, we have developed a graphical tool, called a metronomogram, that we propose will allow us to optimize dosing frequencies and total course durations for clinical benefit.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Neoplasias
/
Antineoplásicos
Tipo de estudio:
Health_economic_evaluation
Límite:
Humans
Idioma:
En
Revista:
Phys Biol
Asunto de la revista:
BIOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos