DNA damage response failure may influence the efficacy of DNA-damaging treatments.
We determined the expression of 16 genes involved in distinct DNA damage response
pathways, in association with the response to standard therapy. Twenty patients with
locoregionally advanced, squamous cell head and neck carcinoma were enrolled. The
treatment included induction chemotherapy (iChT) with docetaxel, cisplatin and 5-fluorouracil
followed by concomitant chemoradiotherapy (ChRT) or radiotherapy (RT) alone. The volumetric
metabolic therapeutic response was determined by [18F]FDG-PET/CT. In the tumor and
matched normal tissues collected before treatment, the gene expressions were examined
via the quantitative real-time polymerase chain reaction (qRT-PCR). The down-regulation
of TP53 was apparently associated with a poor response to iChT, its up-regulation
with complete regression in 2 cases. 7 cases with down-regulated REV1 expression showed
complete regression after ChRT/RT, while 1 case with REV1 overexpression was resistant
to RT. The overexpression of WRN was an independent predictor of tumor relapse. Our
results suggest that an altered expression of REV1 predicts sensitivity to RT, while
WRN overexpression is an unfavorable prognostic factor.