The evolutionary dynamics of a system of cancerous cells in a model of chronic myeloid leukemia (CML) is investigated by a statistical approach. Cancer progression is explored by applying a Monte Carlo method to simulate the stochastic behavior of cell reproduction and death in a population of blood cells which can experience genetic mutations. In CML front line therapy is represented by the tyrosine kinase inhibitor imatinib which strongly affects the reproduction of leukemic cells only. In this work, we analyze the effects of a targeted therapy on the evolutionary dynamics of normal, first-mutant and cancerous cell populations. Several scenarios of the evolutionary dynamics of imatinib-treated leukemic cells are described as a consequence of the efficacy of the different modelled therapies. We show how the patient response to the therapy changes when a high value of the mutation rate from healthy to cancerous cells is present. Our results are in agreement with clinical observations. Unfortunately, development of resistance to imatinib is observed in a fraction of patients, whose blood cells are characterized by an increasing number of genetic alterations. We find that the occurrence of resistance to the therapy can be related to a progressive increase of deleterious mutations.

Pizzolato, N., Valenti, D., Persano Adorno, D., Spagnolo, B. (2009). Evolutionary dynamics of imatinib-treated leukemic cells by stochastic approach. CENTRAL EUROPEAN JOURNAL OF PHYSICS, 7(3), 541-548 [10.2478/s11534-009-0020-1].

Evolutionary dynamics of imatinib-treated leukemic cells by stochastic approach

PIZZOLATO, Nicola;VALENTI, Davide;PERSANO ADORNO, Dominique;SPAGNOLO, Bernardo
2009-01-01

Abstract

The evolutionary dynamics of a system of cancerous cells in a model of chronic myeloid leukemia (CML) is investigated by a statistical approach. Cancer progression is explored by applying a Monte Carlo method to simulate the stochastic behavior of cell reproduction and death in a population of blood cells which can experience genetic mutations. In CML front line therapy is represented by the tyrosine kinase inhibitor imatinib which strongly affects the reproduction of leukemic cells only. In this work, we analyze the effects of a targeted therapy on the evolutionary dynamics of normal, first-mutant and cancerous cell populations. Several scenarios of the evolutionary dynamics of imatinib-treated leukemic cells are described as a consequence of the efficacy of the different modelled therapies. We show how the patient response to the therapy changes when a high value of the mutation rate from healthy to cancerous cells is present. Our results are in agreement with clinical observations. Unfortunately, development of resistance to imatinib is observed in a fraction of patients, whose blood cells are characterized by an increasing number of genetic alterations. We find that the occurrence of resistance to the therapy can be related to a progressive increase of deleterious mutations.
2009
Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin)
Pizzolato, N., Valenti, D., Persano Adorno, D., Spagnolo, B. (2009). Evolutionary dynamics of imatinib-treated leukemic cells by stochastic approach. CENTRAL EUROPEAN JOURNAL OF PHYSICS, 7(3), 541-548 [10.2478/s11534-009-0020-1].
File in questo prodotto:
File Dimensione Formato  
CEJP_7_541_2009.pdf

Solo gestori archvio

Descrizione: Articolo
Dimensione 1.15 MB
Formato Adobe PDF
1.15 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/44966
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 9
social impact