Schedule-dependent increased efficiency of pemetrexed-ionizing radiation combination therapy elicits a differential DNA damage response in lung cancer cells.

ABSTRACT:

Background

Lung cancer causes the most cancer deaths worldwide, thus there is a urgent need to develop new treatment options. Concurrent chemoradiotherapy has become a common strategy for the treatment of non-resectable solid tumors including non-small cell lung cancer. Pemetrexed is a folic acid antagonist that inhibits the synthesis of precursor nucleotides, whereas ionizing radiation induces DNA damage, the repair of which is dependent on sufficiently high nucleotide levels. In the clinical setting, the pemetrexed-ionizing radiation combination therapy is administered concomitantly. We hypothesized that prolonged pretreatment with pemetrexed could be beneficial, as prior depletion of nucleotide pools could sensitize cancer cells to subsequent irradiation.

Methods

Non-smal

SUBMITTER: Dorn P 

PROVIDER: S-EPMC5010745 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature