Patient-Specific Tumor Growth Trajectories Determine Persistent and Resistant Cancer Cell Populations during Treatment with Targeted Therapies.

ABSTRACT: The importance of preexisting versus acquired drug resistance in patients with cancer treated with small-molecule tyrosine kinase inhibitors (TKI) remains controversial. The goal of this study is to provide a general estimate of the size and dynamics of a preexisting, drug-resistant tumor cell population versus a slow-growing persister population that is the precursor of acquired TKI resistance. We describe a general model of resistance development, including persister evolution and preexisting resistance, solely based on the macroscopic trajectory of tumor burden during treatment. We applied the model to 20 tumor volume trajectories of EGFR-mutant lung cancer patients treated with the TKI erlotinib. Under the assumption of only preexisting resistant cells or only persister evolution, it i

SUBMITTER: Grassberger C 

PROVIDER: S-EPMC6635042 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature