Cyclic treatment
strategies in Chronic Myeloid Leukemia (CML) are characterized by
alternating applications of two (or more) different drugs, given one
at a time. One of the main causes for treatment failure in CML is the
generation of drug resistance by mutations of cancerous cells. We use
mathematical methods to develop general guidelines on optimal cyclic
treatment scheduling, with the aim of minimizing the resistance
generation. We define a condition on the drugs' potencies which allows
for a relatively successful application of cyclic therapies. We find
that the best strategy is to start with the stronger drug, but use
longer cycle durations for the weaker drug. We further investigate the
situation where a degree of cross-resistance is present, such that
certain mutations cause cells to become resistant to both drugs
simultaneously.
Citation: Natalia L. Komarova. Mathematical modeling of cyclic treatments of chronic myeloid leukemia[J]. Mathematical Biosciences and Engineering, 2011, 8(2): 289-306. doi: 10.3934/mbe.2011.8.289
Abstract
Cyclic treatment
strategies in Chronic Myeloid Leukemia (CML) are characterized by
alternating applications of two (or more) different drugs, given one
at a time. One of the main causes for treatment failure in CML is the
generation of drug resistance by mutations of cancerous cells. We use
mathematical methods to develop general guidelines on optimal cyclic
treatment scheduling, with the aim of minimizing the resistance
generation. We define a condition on the drugs' potencies which allows
for a relatively successful application of cyclic therapies. We find
that the best strategy is to start with the stronger drug, but use
longer cycle durations for the weaker drug. We further investigate the
situation where a degree of cross-resistance is present, such that
certain mutations cause cells to become resistant to both drugs
simultaneously.