Lung tumours may contain a mix of drug-resistant and drug-sensitive cells. Modified drug regimens could exploit this to delay the emergence of resistant tumours.

Certain non-small-cell lung cancers commonly acquire drug resistance, most often through a mutation called T790M in the gene EGFR. Franziska Michor at the Dana-Farber Cancer Institute in Boston, Massachusetts, William Pao at the Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, and their team cultured resistant and non-resistant cells and found that those with the T790M mutation grew more slowly than drug-sensitive cells. Populations containing resistant cells also regained sensitivity when drug treatment was withdrawn. This, along with data from clinical trials, led the authors to suggest that some resistant tumours still contain drug-sensitive cells that can repopulate the tumour when a drug is taken away.

The authors incorporated these data in a mathematical model to predict tumour behaviour. They estimate that, after drug withdrawal, an in vitro population in which 87.5% of cells are resistant would take 35–40 days to shift to just 1% resistant cells. They propose adding a weekly high-dose drug pulse to the daily low-dose regimen to delay resistance.

Sci. Transl. Med. 3, 90ra59 (2011)