Dynamics of cancer recurrence

Abstract

Mutation-induced drug resistance in cancer often causes the failure of therapies and cancer recurrence, despite an initial tumor reduction. The timing of such cancer recurrence is governed by a balance between several factors such as initial tumor size, mutation rates and growth kinetics of drug-sensitive and resistance cells. To study this phenomenon we characterize the dynamics of escape from extinction of a subcritical branching process, where the establishment of a clone of escape mutants can lead to total population growth after the initial decline. We derive uniform in-time approximations for the paths of the escape process and its components, in the limit as the initial population size tends to infinity and the mutation rate tends to zero. In addition, two stochastic times important in cancer recurrence will be characterized: (i) the time at which the total population size first begins to rebound (i.e., become supercritical) during treatment, and (ii) the first time at which the resistant cell population begins to dominate the tumor.Comment: Published in at http://dx.doi.org/10.1214/12-AAP876 the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org